5-132813626-C-T

Variant names:

• chr5-132813626-C-T
• rs1758326818
• NM_175873.6:c.5C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175873.6(SOWAHA):​c.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000166 in 1,207,356 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: SOWAHA NM_175873.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.07
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22756037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175873.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOWAHA	NM_175873.6	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 1	NP_787069.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOWAHA	ENST00000378693.4	TSL:6 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 1	ENSP00000367965.2	Q2M3V2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000166 AC: 2 AN: 1207356 Hom.: 0 Cov.: 30 AF XY: 0.00000170 AC XY: 1 AN XY: 587676

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23542

American (AMR) AF: 0.00 AC: 0 AN: 9968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16158

East Asian (EAS) AF: 0.00 AC: 0 AN: 27060

South Asian (SAS) AF: 0.00 AC: 0 AN: 47884

European-Finnish (FIN) AF: 0.0000279 AC: 1 AN: 35876

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3354

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 994432

Other (OTH) AF: 0.00 AC: 0 AN: 49082

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Benign	0.96
Eigen	Benign	-0.064
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.21	N
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.96	T
PhyloP100		2.1
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.098	T
Vest4		0.16
MutPred		0.26		Loss of disorder (P = 0.0565)
MVP		0.12
ClinPred		0.56	D
GERP RS		4.0
PromoterAI		-0.21	Neutral
gMVP		0.62
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs1758326818; hg19: chr5-132149318;