chr4-76896267-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001029870.3(SOWAHB):​c.1583G>T​(p.Arg528Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000413 in 1,452,076 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.000041 ( 1 hom. )

Consequence

SOWAHB
NM_001029870.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.452
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3530571).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SOWAHBNM_001029870.3 linkc.1583G>T p.Arg528Leu 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.1583G>T p.Arg528Leu missense_variant Exon 1 of 1 6 NM_001029870.3 ENSP00000334879.2 A6NEL2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000767
AC:
19
AN:
247764
Hom.:
0
AF XY:
0.0000968
AC XY:
13
AN XY:
134236
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:
0.000595
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000167
GnomAD4 exome
AF:
0.0000413
AC:
60
AN:
1452076
Hom.:
1
Cov.:
33
AF XY:
0.0000541
AC XY:
39
AN XY:
720914
show subpopulations
Gnomad4 AFR exome
AF:
0.0000303
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000653
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000502
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000741
AC:
9
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
Jul 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1583G>T (p.R528L) alteration is located in exon 1 (coding exon 1) of the SOWAHB gene. This alteration results from a G to T substitution at nucleotide position 1583, causing the arginine (R) at amino acid position 528 to be replaced by a leucine (L). 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
0.29
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.053
T
Eigen
Benign
0.13
Eigen_PC
Benign
0.046
FATHMM_MKL
Benign
0.50
D
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.35
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.3
D
REVEL
Benign
0.17
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.017
D
Polyphen
1.0
D
Vest4
0.58
MutPred
0.32
Loss of glycosylation at P527 (P = 0.0079);
MVP
0.28
ClinPred
0.35
T
GERP RS
5.0
Varity_R
0.31
gMVP
0.43

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: rs199835098; hg19: chr4-77817420; API