Genetic Variant SOWAHA:p.Pro85His (chr5-132813875-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_175873.6(SOWAHA):c.254C>A(p.Pro85His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,548,518 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P85S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 1 hom. )

Consequence

SOWAHA
NM_175873.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

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 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=0.012470573).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOWAHA	NM_175873.6 link	c.254C>A	p.Pro85His	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.254C>A	p.Pro85His	missense_variant	Exon 1 of 1	6	NM_175873.6	ENSP00000367965.2		Q2M3V2

Frequencies

GnomAD3 genomes

AF:

0.000362

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000597

AC:

AN:

142302

Hom.:

AF XY:

0.000498

AC XY:

AN XY:

76302

show subpopulations

Gnomad AFR exome

AF:

0.000742

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.000244

Gnomad EAS exome

AF:

0.0000955

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.000488

GnomAD4 exome

AF:

0.000486

AC:

678

AN:

1396332

Hom.:

Cov.:

AF XY:

0.000499

AC XY:

344

AN XY:

688710

show subpopulations

Gnomad4 AFR exome

AF:

0.000160

Gnomad4 AMR exome

AF:

0.000645

Gnomad4 ASJ exome

AF:

0.000677

Gnomad4 EAS exome

AF:

0.0000281

Gnomad4 SAS exome

AF:

0.000215

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000529

Gnomad4 OTH exome

AF:

0.000294

GnomAD4 genome

AF:

0.000361

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000804

Hom.:

Bravo

AF:

0.000570

ExAC

AF:

0.000274

AC:

Asia WGS

AF:

0.000579

AC:

AN:

3470

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.254C>A (p.P85H) alteration is located in exon 1 (coding exon 1) of the SOWAHA gene. This alteration results from a C to A substitution at nucleotide position 254, causing the proline (P) at amino acid position 85 to be replaced by a histidine (H). 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

0.097

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.93

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.14

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.0

REVEL

Benign

0.010

Sift

Benign

0.37

Sift4G

Benign

0.078

Vest4

0.15

MVP

0.13

ClinPred

0.0067

GERP RS

2.7

gMVP

0.17

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