Genetic Variant SOBP:p.Ser683Cys (chr6-107634891-A-T) – 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_018013.4(SOBP):c.2047A>T(p.Ser683Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000859 in 1,164,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. S683G) has been classified as Benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 8.6e-7 ( 0 hom. )

Consequence

SOBP
NM_018013.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.03

Publications

0 publications found

Variant links:

Genes affected

SOBP (HGNC:29256): (sine oculis binding protein homolog) The protein encoded by this gene is a nuclear zinc finger protein that is involved in development of the cochlea. Defects in this gene have also been linked to intellectual disability. [provided by RefSeq, Mar 2011]

SOBP Gene-Disease associations (from GenCC):

intellectual disability, anterior maxillary protrusion, and strabismus
Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
syndromic intellectual disability
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SOBP links:

Genome browser will be placed here

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=0.12931728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4 link	c.2047A>T	p.Ser683Cys	missense_variant	Exon 6 of 7	ENST00000317357.10	NP_060483.3	A7XYQ1Q24K27

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10 link	c.2047A>T	p.Ser683Cys	missense_variant	Exon 6 of 7	5	NM_018013.4	ENSP00000318900.5		A7XYQ1
SOBP	ENST00000494935.1 link	n.-99A>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.59e-7

AC:

AN:

1164220

Hom.:

Cov.:

AF XY:

0.00000176

AC XY:

AN XY:

568764

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23928

American (AMR)

AF:

0.00

AC:

AN:

21878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18430

East Asian (EAS)

AF:

0.00

AC:

AN:

22154

South Asian (SAS)

AF:

0.00

AC:

AN:

50344

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3276

European-Non Finnish (NFE)

AF:

0.00000105

AC:

AN:

954744

Other (OTH)

AF:

0.00

AC:

AN:

45174

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

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

0.093

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.079

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.23

M_CAP

Benign

0.059

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

5.0

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.2

REVEL

Benign

0.094

Sift

Uncertain

0.015

Sift4G

Uncertain

0.039

Polyphen

0.60

Vest4

0.12

MutPred

0.23

Gain of catalytic residue at P682 (P = 0.0069);

MVP

0.048

ClinPred

0.32

GERP RS

1.9

Varity_R

0.11

gMVP

0.19

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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