7-29883967-C-A

Variant names:

• chr7-29883967-C-A
• rs943086410
• NM_001080529.3:c.473C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080529.3(WIPF3):​c.473C>A​(p.Ala158Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.204

Genes affected

WIPF3 (HGNC:22004): (WAS/WASL interacting protein family member 3) Predicted to enable SH3 domain binding activity and actin binding activity. Predicted to be involved in actin filament-based movement. Predicted to be located in cytosol. Predicted to be active in actin filament. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.056577265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF3	NM_001080529.3	c.473C>A	p.Ala158Glu	missense_variant	Exon 5 of 9	ENST00000242140.10	NP_001073998.2
WIPF3	NM_001391973.1	c.473C>A	p.Ala158Glu	missense_variant	Exon 5 of 8		NP_001378902.1
WIPF3	XM_017012522.2	c.440C>A	p.Ala147Glu	missense_variant	Exon 4 of 8		XP_016868011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIPF3	ENST00000242140.10	c.473C>A	p.Ala158Glu	missense_variant	Exon 5 of 9	5	NM_001080529.3	ENSP00000242140.6
WIPF3	ENST00000409123.5	c.473C>A	p.Ala158Glu	missense_variant	Exon 5 of 8	5		ENSP00000386790.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.17e-7 AC: 1 AN: 1395522 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 688478

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.28e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.473C>A (p.A158E) alteration is located in exon 5 (coding exon 4) of the WIPF3 gene. This alteration results from a C to A substitution at nucleotide position 473, causing the alanine (A) at amino acid position 158 to be replaced by a glutamic acid (E). 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	0.16
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.83
DEOGEN2	Benign	0.19	.;T;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.50	T;T;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	.;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.0080
Sift	Uncertain	0.0080	D;D;D
Sift4G	Benign	0.69	T;T;T
Polyphen		0.36	.;B;B
Vest4		0.16
MutPred		0.22		Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);
MVP		0.099
MPC		0.24
ClinPred		0.13	T
GERP RS		0.30
Varity_R		0.16
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs943086410; hg19: chr7-29923583;