7-29884129-T-C

Position:

• chr7-29884129-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001080529.3(WIPF3):​c.635T>C​(p.Leu212Pro) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033608854).
• BP6: Variant 7-29884129-T-C is Benign according to our data. Variant chr7-29884129-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2283628.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIPF3	NM_001080529.3	c.635T>C	p.Leu212Pro	missense_variant	5/9	ENST00000242140.10
WIPF3	NM_001391973.1	c.635T>C	p.Leu212Pro	missense_variant	5/8
WIPF3	XM_017012522.2	c.602T>C	p.Leu201Pro	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIPF3	ENST00000242140.10	c.635T>C	p.Leu212Pro	missense_variant	5/9	5	NM_001080529.3	P5
WIPF3	ENST00000409123.5	c.635T>C	p.Leu212Pro	missense_variant	5/8	5		A2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 13, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.75
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00086	N
LIST_S2	Benign	0.26	T;T;.
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.034	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	1.8	N;N;N
REVEL	Benign	0.031
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.35	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.028
MutPred		0.28		Loss of stability (P = 0.0287);Loss of stability (P = 0.0287);Loss of stability (P = 0.0287);
MVP		0.055
MPC		0.13
ClinPred		0.13	T
GERP RS		1.6
Varity_R		0.047
gMVP		0.12

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-29923745;