7-29875897-T-C

Variant names:

• chr7-29875897-T-C
• NM_001080529.3:c.158T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001080529.3(WIPF3):​c.158T>C​(p.Ile53Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF3	NM_001080529.3	c.158T>C	p.Ile53Thr	missense_variant	Exon 3 of 9	ENST00000242140.10	NP_001073998.2
WIPF3	NM_001391973.1	c.158T>C	p.Ile53Thr	missense_variant	Exon 3 of 8		NP_001378902.1
WIPF3	XM_017012522.2	c.125T>C	p.Ile42Thr	missense_variant	Exon 2 of 8		XP_016868011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIPF3	ENST00000242140.10	c.158T>C	p.Ile53Thr	missense_variant	Exon 3 of 9	5	NM_001080529.3	ENSP00000242140.6
WIPF3	ENST00000409123.5	c.158T>C	p.Ile53Thr	missense_variant	Exon 3 of 8	5		ENSP00000386790.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.158T>C (p.I53T) alteration is located in exon 3 (coding exon 2) of the WIPF3 gene. This alteration results from a T to C substitution at nucleotide position 158, causing the isoleucine (I) at amino acid position 53 to be replaced by a threonine (T). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.56
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.83	.;D;D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D;D;.
M_CAP	Pathogenic	0.59	D
MetaRNN	Pathogenic	0.89	D;D;D
MetaSVM	Pathogenic	0.91	D
MutationAssessor	Pathogenic	3.8	.;H;H
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Pathogenic	0.86
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.94
MutPred		0.55		Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);
MVP		0.93
MPC		0.50
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.69
gMVP		0.64

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: chr7-29915513;