Genetic Variant SOWAHA:p.Pro85Ser (chr5-132813874-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_175873.6(SOWAHA):c.253C>T(p.Pro85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,548,236 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 2 hom. )

Consequence

SOWAHA
NM_175873.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.290

Variant links:

Genes affected

SOWAHA (HGNC:27033): (sosondowah ankyrin repeat domain family member A)

SOWAHA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041429996).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOWAHA	NM_175873.6 link	c.253C>T	p.Pro85Ser	missense_variant	Exon 1 of 1	ENST00000378693.4	NP_787069.4	Q2M3V2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOWAHA	ENST00000378693.4 link	c.253C>T	p.Pro85Ser	missense_variant	Exon 1 of 1	6	NM_175873.6	ENSP00000367965.2		Q2M3V2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000815

AC:

116

AN:

142286

Hom.:

AF XY:

0.000721

AC XY:

AN XY:

76310

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00250

Gnomad ASJ exome

AF:

0.00402

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000885

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000119

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.000171

AC:

239

AN:

1396048

Hom.:

Cov.:

AF XY:

0.000170

AC XY:

117

AN XY:

688570

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00213

Gnomad4 ASJ exome

AF:

0.00370

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000758

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000380

Gnomad4 OTH exome

AF:

0.000363

GnomAD4 genome

AF:

0.000151

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000226

Hom.:

Bravo

AF:

0.000325

ExAC

AF:

0.000378

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 05, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.253C>T (p.P85S) alteration is located in exon 1 (coding exon 1) of the SOWAHA gene. This alteration results from a C to T substitution at nucleotide position 253, causing the proline (P) at amino acid position 85 to be replaced by a serine (S). 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

0.075

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

3.7

DANN

Benign

0.84

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.21

M_CAP

Benign

0.077

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.58

REVEL

Benign

0.049

Sift

Benign

0.23

Sift4G

Benign

0.072

Vest4

0.085

MutPred

0.35

Loss of catalytic residue at P85 (P = 7e-04);

MVP

0.099

ClinPred

0.015

GERP RS

3.6

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over