chr7-29884026-A-T

Variant names:

• chr7-29884026-A-T
• rs776026225
• NM_001080529.3:c.532A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001080529.3(WIPF3):​c.532A>T​(p.Thr178Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000364 in 549,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000036 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0650
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05404678).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080529.3. 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
	WIPF3	NM_001080529.3	MANE Select	c.532A>T	p.Thr178Ser	missense	Exon 5 of 9	NP_001073998.2	A6NGB9
	WIPF3	NM_001391973.1		c.532A>T	p.Thr178Ser	missense	Exon 5 of 8	NP_001378902.1	A0A0A0MSG0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF3	ENST00000242140.10	TSL:5 MANE Select	c.532A>T	p.Thr178Ser	missense	Exon 5 of 9	ENSP00000242140.6	A6NGB9
	WIPF3	ENST00000409123.5	TSL:5	c.532A>T	p.Thr178Ser	missense	Exon 5 of 8	ENSP00000386790.1	A0A0A0MSG0
	WIPF3	ENST00000869766.1		c.532A>T	p.Thr178Ser	missense	Exon 5 of 9	ENSP00000539825.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 10880 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000364 AC: 2 AN: 549466 Hom.: 0 Cov.: 22 AF XY: 0.00000377 AC XY: 1 AN XY: 265504

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 11404

American (AMR) AF: 0.00 AC: 0 AN: 6134

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6868

East Asian (EAS) AF: 0.00 AC: 0 AN: 4380

South Asian (SAS) AF: 0.00 AC: 0 AN: 28302

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13522

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1374

European-Non Finnish (NFE) AF: 0.00000438 AC: 2 AN: 456558

Other (OTH) AF: 0.00 AC: 0 AN: 20924

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000812204), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10880 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 5258

African (AFR) AF: 0.00 AC: 0 AN: 2646

American (AMR) AF: 0.00 AC: 0 AN: 1362

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 248

East Asian (EAS) AF: 0.00 AC: 0 AN: 242

South Asian (SAS) AF: 0.00 AC: 0 AN: 264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 5178

Other (OTH) AF: 0.00 AC: 0 AN: 146

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.7
DANN	Benign	0.53
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.065
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.016
Sift	Benign	0.52	T
Sift4G	Benign	0.94	T
Polyphen		0.14	B
Vest4		0.13
MutPred		0.39		Loss of catalytic residue at T178 (P = 0.1187)
MVP		0.030
MPC		0.26
ClinPred		0.070	T
GERP RS		-2.6
Varity_R		0.080
gMVP		0.12
Mutation Taster		=100/0	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: rs776026225; hg19: chr7-29923642;