Genetic Variant NM_002968.3:c.478G>C (chr16-51141744-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002968.3(SALL1):c.478G>C(p.Gly160Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. G160S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SALL1
NM_002968.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.86

Publications

0 publications found

Variant links:

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

SALL1 links:

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ACMG classification

Classification was made for transcript

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=0.09379807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SALL1	NM_002968.3 link	c.478G>C	p.Gly160Arg	missense_variant	Exon 2 of 3	ENST00000251020.9	NP_002959.2	Q9NSC2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SALL1	ENST00000251020.9 link	c.478G>C	p.Gly160Arg	missense_variant	Exon 2 of 3	1	NM_002968.3	ENSP00000251020.4		Q9NSC2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1428926

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

710698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32714

American (AMR)

AF:

0.00

AC:

AN:

43538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25464

East Asian (EAS)

AF:

0.00

AC:

AN:

38532

South Asian (SAS)

AF:

0.0000238

AC:

AN:

83984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51878

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5450

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088550

Other (OTH)

AF:

0.00

AC:

AN:

58816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.79

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.21

.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.34

T;T;T

M_CAP

Benign

0.00086

MetaRNN

Benign

0.094

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.49

.;N;.

PhyloP100

1.9

PrimateAI

Benign

0.34

PROVEAN

Benign

0.13

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.53

T;T;T

Sift4G

Benign

0.50

T;T;.

Polyphen

0.62

.;P;.

Vest4

0.13

MutPred

0.29

.;Gain of solvent accessibility (P = 0.0037);.;

MVP

0.38

MPC

0.24

ClinPred

0.12

GERP RS

-1.6

Varity_R

0.036

gMVP

0.14

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over