dbSNP rs267607078: SOBP:p.Arg661Gly (chr6-107634825-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_018013.4(SOBP):c.1981C>G(p.Arg661Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,256,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

SOBP
NM_018013.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.786

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOBP	NM_018013.4 link	c.1981C>G	p.Arg661Gly	missense_variant	Exon 6 of 7	ENST00000317357.10	NP_060483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOBP	ENST00000317357.10 link	c.1981C>G	p.Arg661Gly	missense_variant	Exon 6 of 7	5	NM_018013.4	ENSP00000318900.5
SOBP	ENST00000494935.1 link	n.-165C>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000159

AC:

AN:

1256960

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

619500

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:

25516

American (AMR)

AF:

0.00

AC:

AN:

24828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20926

East Asian (EAS)

AF:

0.00

AC:

AN:

25296

South Asian (SAS)

AF:

0.00

AC:

AN:

66330

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4020

European-Non Finnish (NFE)

AF:

0.00000198

AC:

AN:

1010122

Other (OTH)

AF:

0.00

AC:

AN:

50518

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.50

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.73

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

0.79

PrimateAI

Pathogenic

0.96

PROVEAN

Benign

-1.7

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.027

Polyphen

0.99

Vest4

0.65

MutPred

0.53

Loss of MoRF binding (P = 0.0493);

MVP

0.17

ClinPred

0.94

GERP RS

3.5

Varity_R

0.35

gMVP

0.39

Mutation Taster

=62/38

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over