4-76896243-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001029870.3(SOWAHB):​c.1607G>A​(p.Gly536Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000772 in 1,593,060 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000077 ( 1 hom. )

Consequence

SOWAHB
NM_001029870.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.677
Variant links:
Genes affected
SOWAHB (HGNC:32958): (sosondowah ankyrin repeat domain family member B)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06328669).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOWAHBNM_001029870.3 linkc.1607G>A p.Gly536Glu 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
SOWAHBENST00000334306.4 linkc.1607G>A p.Gly536Glu missense_variant Exon 1 of 1 6 NM_001029870.3 ENSP00000334879.2 A6NEL2

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152250
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000121
AC:
29
AN:
240572
Hom.:
0
AF XY:
0.000146
AC XY:
19
AN XY:
130458
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000992
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000770
AC:
111
AN:
1440692
Hom.:
1
Cov.:
32
AF XY:
0.000113
AC XY:
81
AN XY:
714314
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.00123
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.09e-7
Gnomad4 OTH exome
AF:
0.0000845
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152368
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74512
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00228
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.000107
AC:
13
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 27, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1607G>A (p.G536E) 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 1607, causing the glycine (G) at amino acid position 536 to be replaced by a glutamic acid (E). 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
0.25
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.0076
T
MetaRNN
Benign
0.063
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-4.0
D
REVEL
Benign
0.18
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.010
D
Polyphen
0.90
P
Vest4
0.58
MutPred
0.42
Gain of glycosylation at S540 (P = 0.0174);
MVP
0.38
ClinPred
0.26
T
GERP RS
5.0
Varity_R
0.34
gMVP
0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs375826911; hg19: chr4-77817396; API