rs4614723

chr16-51137264-C-Gchr16-51137264-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002968.3(SALL1):c.3823G>C(p.Val1275Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1275I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: SALL1 NM_002968.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.725

Genes affected

SALL1 (HGNC:10524): (spalt like transcription factor 1) The protein encoded by this gene is a zinc finger transcriptional repressor and may be part of the NuRD histone deacetylase complex (HDAC). Defects in this gene are a cause of Townes-Brocks syndrome (TBS) as well as bronchio-oto-renal syndrome (BOR). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03470859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SALL1	NM_002968.3	c.3823G>C	p.Val1275Leu	missense_variant	3/3	ENST00000251020.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SALL1	ENST00000251020.9	c.3823G>C	p.Val1275Leu	missense_variant	3/3	1	NM_002968.3	P2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	2.4
Dann	Benign	0.82
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.035	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;N;N;N
PROVEAN	Benign	0.54	N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T
Sift4G	Benign	0.75	T;T
Polyphen		0.0	.;B
Vest4		0.034
MutPred		0.20		.;Loss of glycosylation at S1276 (P = 0.1192);
MVP		0.093
MPC		0.20
ClinPred		0.056	T
GERP RS		3.5
Varity_R		0.088
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4614723; hg19: chr16-51171175;