NM_002968.3:c.3847G>A

Variant names:

• chr16-51137240-C-T
• rs1962320101
• NM_002968.3:c.3847G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002968.3(SALL1):​c.3847G>A​(p.Glu1283Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SALL1 NM_002968.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.11
• Publications: 0 publications found

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]

SALL1 Gene-Disease associations (from GenCC):

• Townes-Brocks syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics
• Townes-Brocks syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21671402).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002968.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	NM_002968.3	MANE Select	c.3847G>A	p.Glu1283Lys	missense	Exon 3 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.3556G>A	p.Glu1186Lys	missense	Exon 3 of 3	NP_001121364.1	Q9NSC2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SALL1	ENST00000251020.9	TSL:1 MANE Select	c.3847G>A	p.Glu1283Lys	missense	Exon 3 of 3	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000566102.1	TSL:1	c.*284G>A		3_prime_UTR	Exon 2 of 2	ENSP00000455582.1	H3BQ32
	SALL1	ENST00000440970.6	TSL:5	c.3847G>A	p.Glu1283Lys	missense	Exon 4 of 4	ENSP00000407914.2	Q9NSC2-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Townes-Brocks syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.1
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.10
Sift	Benign	0.13	T
Sift4G	Benign	0.062	T
Polyphen		0.88	P
Vest4		0.26
MutPred		0.33		Gain of ubiquitination at E1283 (P = 0.0048)
MVP		0.21
MPC		0.27
ClinPred		0.82	D
GERP RS		5.8
Varity_R		0.28
gMVP		0.46
Mutation Taster		=57/43	polymorphism

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

Other links and lift over

dbSNP: rs1962320101; hg19: chr16-51171151; COSMIC: COSV106335608; COSMIC: COSV106335608;