7-29883879-C-G

Variant names:

• chr7-29883879-C-G
• rs1290480775
• NM_001080529.3:c.385C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080529.3(WIPF3):​c.385C>G​(p.Arg129Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,416,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.946

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF3	NM_001080529.3	c.385C>G	p.Arg129Gly	missense_variant	Exon 5 of 9	ENST00000242140.10	NP_001073998.2
WIPF3	NM_001391973.1	c.385C>G	p.Arg129Gly	missense_variant	Exon 5 of 8		NP_001378902.1
WIPF3	XM_017012522.2	c.352C>G	p.Arg118Gly	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.385C>G	p.Arg129Gly	missense_variant	Exon 5 of 9	5	NM_001080529.3	ENSP00000242140.6
WIPF3	ENST00000409123.5	c.385C>G	p.Arg129Gly	missense_variant	Exon 5 of 8	5		ENSP00000386790.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1416678 Hom.: 0 Cov.: 32 AF XY: 0.00000143 AC XY: 1 AN XY: 698390

Gnomad4 AFR exome AF: 0.0000306

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: 0.00000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.385C>G (p.R129G) alteration is located in exon 5 (coding exon 4) of the WIPF3 gene. This alteration results from a C to G substitution at nucleotide position 385, causing the arginine (R) at amino acid position 129 to be replaced by a glycine (G). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	.;D;D
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.83	T;T;.
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.29	T
MutationAssessor	Uncertain	2.6	.;M;M
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.2	D;D;D
REVEL	Benign	0.19
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.029	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.48
MVP		0.53
MPC		0.16
ClinPred		0.95	D
GERP RS		1.7
Varity_R		0.29
gMVP		0.42

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

Other links and lift over

dbSNP: rs1290480775; hg19: chr7-29923495;