NM_002968.3(SALL1):c.3128_3129del (p.Asn1043fs) AND Townes syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 15, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003758218.2

Allele description [Variation Report for NM_002968.3(SALL1):c.3128_3129del (p.Asn1043fs)]

NM_002968.3(SALL1):c.3128_3129del (p.Asn1043fs)

Gene:

SALL1:spalt like transcription factor 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

16q12.1

Genomic location:

Preferred name:

NM_002968.3(SALL1):c.3128_3129del (p.Asn1043fs)

HGVS:

NC_000016.10:g.51139093_51139094del
NG_007990.1:g.17179_17180del
NM_001127892.2:c.2837_2838del
NM_002968.3:c.3128_3129delMANE SELECT
NP_001121364.1:p.Asn946fs
NP_002959.2:p.Asn1043Ilefs
NP_002959.2:p.Asn1043fs
LRG_674t1:c.3128_3129del
LRG_674:g.17179_17180del
LRG_674p1:p.Asn1043Ilefs
NC_000016.9:g.51173004_51173005del
NM_002968.2:c.3128_3129delAT

Protein change:

N1043fs

Molecular consequence:

NM_001127892.2:c.2837_2838del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002968.3:c.3128_3129del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Townes syndrome (TBS)
Synonyms:: Townes-Brocks syndrome
Identifiers:: MONDO: MONDO:0007142; MeSH: C536974; MedGen: C0265246; Orphanet: 857; OMIM: PS107480

Recent activity

Clear Turn Off Turn On

Component Of for Nucleotide (Select 13293539) (4)
Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004422824	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 15, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9973281, 12915476, 16088922, 23069192, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004422824

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 15, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular analysis of SALL1 mutations in Townes-Brocks syndrome.

Kohlhase J, Taschner PE, Burfeind P, Pasche B, Newman B, Blanck C, Breuning MH, ten Kate LP, Maaswinkel-Mooy P, Mitulla B, Seidel J, Kirkpatrick SJ, Pauli RM, Wargowski DS, Devriendt K, Proesmans W, Gabrielli O, Coppa GV, Wesby-van Swaay E, Trembath RC, Schinzel AA, Reardon W, et al.

Am J Hum Genet. 1999 Feb;64(2):435-45.

PubMed [citation]

PMID:: 9973281
PMCID:: PMC1377753

Expression of a truncated Sall1 transcriptional repressor is responsible for Townes-Brocks syndrome birth defects.

Kiefer SM, Ohlemiller KK, Yang J, McDill BW, Kohlhase J, Rauchman M.

Hum Mol Genet. 2003 Sep 1;12(17):2221-7. Epub 2003 Jul 15.

PubMed [citation]

PMID:: 12915476

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004422824.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with SALL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn1043Ilefs*19) in the SALL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SALL1 are known to be pathogenic (PMID: 9973281, 12915476, 16088922, 23069192).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine