chr16-51137264-C-T

Variant names:

• chr16-51137264-C-T
• rs4614723
• NM_002968.3:c.3823G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002968.3(SALL1):​c.3823G>A​(p.Val1275Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.998 in 1,614,030 control chromosomes in the GnomAD database, including 803,803 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74519 hom., cov: 29)
  • Exomes 𝑓: 1.0 (729284 hom.)
• Consequence: SALL1 NM_002968.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.725
• Publications: 31 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.5106074E-7).
• BP6: Variant 16-51137264-C-T is Benign according to our data. Variant chr16-51137264-C-T is described in ClinVar as Benign. ClinVar VariationId is 258871.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

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.3823G>A	p.Val1275Ile	missense	Exon 3 of 3	NP_002959.2	Q9NSC2-1
	SALL1	NM_001127892.2		c.3532G>A	p.Val1178Ile	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.3823G>A	p.Val1275Ile	missense	Exon 3 of 3	ENSP00000251020.4	Q9NSC2-1
	SALL1	ENST00000566102.1	TSL:1	c.*260G>A		3_prime_UTR	Exon 2 of 2	ENSP00000455582.1	H3BQ32
	SALL1	ENST00000440970.6	TSL:5	c.3823G>A	p.Val1275Ile	missense	Exon 4 of 4	ENSP00000407914.2	Q9NSC2-1

Frequencies

GnomAD3 genomes AF: 0.990 AC: 150439 AN: 152024 Hom.: 74463 Cov.: 29

Gnomad AFR AF: 0.964

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.995

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.993

GnomAD2 exomes AF: 0.997 AC: 250745 AN: 251490 AF XY: 0.998

Gnomad AFR exome AF: 0.961

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 0.999

GnomAD4 exome AF: 0.999 AC: 1460195 AN: 1461888 Hom.: 729284 Cov.: 63 AF XY: 0.999 AC XY: 726514 AN XY: 727246

African (AFR) AF: 0.961 AC: 32186 AN: 33478

American (AMR) AF: 0.997 AC: 44611 AN: 44724

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26135 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39700 AN: 39700

South Asian (SAS) AF: 1.00 AC: 86248 AN: 86258

European-Finnish (FIN) AF: 1.00 AC: 53420 AN: 53420

Middle Eastern (MID) AF: 0.998 AC: 5758 AN: 5768

European-Non Finnish (NFE) AF: 1.00 AC: 1111904 AN: 1112008

Other (OTH) AF: 0.997 AC: 60233 AN: 60396

GnomAD4 genome AF: 0.990 AC: 150553 AN: 152142 Hom.: 74519 Cov.: 29 AF XY: 0.990 AC XY: 73641 AN XY: 74366

African (AFR) AF: 0.964 AC: 40021 AN: 41502

American (AMR) AF: 0.995 AC: 15213 AN: 15290

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3470 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5146 AN: 5146

South Asian (SAS) AF: 1.00 AC: 4788 AN: 4790

European-Finnish (FIN) AF: 1.00 AC: 10610 AN: 10610

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68014 AN: 68028

Other (OTH) AF: 0.993 AC: 2086 AN: 2100

Alfa AF: 0.996 Hom.: 54146

Bravo AF: 0.989

TwinsUK AF: 1.00 AC: 3708

ALSPAC AF: 0.999 AC: 3852

ESP6500AA AF: 0.966 AC: 4245

ESP6500EA AF: 1.00 AC: 8600

ExAC AF: 0.997 AC: 120985

Asia WGS AF: 0.998 AC: 3472 AN: 3478

EpiCase AF: 1.00

EpiControl AF: 1.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Townes-Brocks syndrome 1 (3)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Townes syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.6
DANN	Benign	0.88
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	5.5e-7	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.95	N
PhyloP100		0.72
PROVEAN	Benign	0.34	N
REVEL	Benign	0.14
Sift	Benign	0.84	T
Sift4G	Benign	0.48	T
Polyphen		0.0	B
Vest4		0.052
MPC		0.16
ClinPred		0.0011	T
GERP RS		3.5
Varity_R		0.044
gMVP		0.18
Mutation Taster		=99/1	polymorphism (auto)

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: rs4614723; hg19: chr16-51171175; COSMIC: COSV107229099; COSMIC: COSV107229099;