4-76896243-C-G

Variant names:

• chr4-76896243-C-G
• rs375826911
• NM_001029870.3:c.1607G>C

Variant summary

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

The NM_001029870.3(SOWAHB):​c.1607G>C​(p.Gly536Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G536E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SOWAHB NM_001029870.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 1 publications found

Genes affected

SOWAHB (HGNC:32958): (sosondowah ankyrin repeat domain family member B)

ENSG00000294131 (HGNC:58823):

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=0.16621271).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029870.3. 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
	SOWAHB	NM_001029870.3	MANE Select	c.1607G>C	p.Gly536Ala	missense	Exon 1 of 1	NP_001025041.1	A6NEL2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOWAHB	ENST00000334306.4	TSL:6 MANE Select	c.1607G>C	p.Gly536Ala	missense	Exon 1 of 1	ENSP00000334879.2	A6NEL2
	ENSG00000294131	ENST00000721349.1		n.206-8386C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000416 AC: 1 AN: 240572 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000908

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.077
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.68
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.12
Sift	Uncertain	0.028	D
Sift4G	Benign	0.069	T
Polyphen		0.98	D
Vest4		0.17
MutPred		0.33		Gain of glycosylation at S540 (P = 0.0174)
MVP		0.50
ClinPred		0.77	D
GERP RS		5.0
Varity_R		0.23
gMVP		0.38
Mutation Taster		=98/2	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: rs375826911; hg19: chr4-77817396;