Genetic Variant NM_001029870.3:c.1987G>A (chr4-76895863-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001029870.3(SOWAHB):c.1987G>A(p.Val663Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SOWAHB
NM_001029870.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.852

Variant links:

Genes affected

SOWAHB (HGNC:32958): (sosondowah ankyrin repeat domain family member B)

SOWAHB links:

ENSG00000294131 (HGNC:):

ENSG00000294131 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30670366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOWAHB	NM_001029870.3 link	c.1987G>A	p.Val663Ile	missense_variant	Exon 1 of 1	ENST00000334306.4	NP_001025041.1	A6NEL2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOWAHB	ENST00000334306.4 link	c.1987G>A	p.Val663Ile	missense_variant	Exon 1 of 1	6	NM_001029870.3	ENSP00000334879.2		A6NEL2
ENSG00000294131	ENST00000721349.1 link	n.205+8554C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 27, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1987G>A (p.V663I) alteration is located in exon 1 (coding exon 1) of the SOWAHB gene. This alteration results from a G to A substitution at nucleotide position 1987, causing the valine (V) at amino acid position 663 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0087

Eigen

Benign

-0.084

Eigen_PC

Benign

-0.082

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.55

M_CAP

Benign

0.0067

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.71

PhyloP100

0.85

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.63

REVEL

Benign

0.060

Sift

Benign

0.082

Sift4G

Uncertain

0.055

Polyphen

0.79

Vest4

0.099

MutPred

0.59

Loss of MoRF binding (P = 0.3252);

MVP

0.59

ClinPred

0.30

GERP RS

3.6

Varity_R

0.051

gMVP

0.42

Mutation Taster

=94/6

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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NM_001029870.3:c.1987G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over