7-29884026-A-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080529.3(WIPF3):​c.532A>C​(p.Thr178Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T178S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.14 (0 hom., cov: 0)
  • Exomes 𝑓: 0.026 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650
• Publications: 1 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019820333).

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>C	p.Thr178Pro	missense	Exon 5 of 9	NP_001073998.2	A6NGB9
	WIPF3	NM_001391973.1		c.532A>C	p.Thr178Pro	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>C	p.Thr178Pro	missense	Exon 5 of 9	ENSP00000242140.6	A6NGB9
	WIPF3	ENST00000409123.5	TSL:5	c.532A>C	p.Thr178Pro	missense	Exon 5 of 8	ENSP00000386790.1	A0A0A0MSG0
	WIPF3	ENST00000869766.1		c.532A>C	p.Thr178Pro	missense	Exon 5 of 9	ENSP00000539825.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 1224 AN: 8504 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.0918

Gnomad SAS AF: 0.0310

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.232 AC: 2988 AN: 12886 AF XY: 0.227

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.225

Gnomad ASJ exome AF: 0.137

Gnomad EAS exome AF: 0.296

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.148

Gnomad OTH exome AF: 0.249

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0263 AC: 14183 AN: 539920 Hom.: 0 Cov.: 22 AF XY: 0.0309 AC XY: 8045 AN XY: 260004

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

African (AFR) AF: 0.0117 AC: 132 AN: 11250

American (AMR) AF: 0.0571 AC: 324 AN: 5670

Ashkenazi Jewish (ASJ) AF: 0.0345 AC: 231 AN: 6692

East Asian (EAS) AF: 0.0253 AC: 109 AN: 4310

South Asian (SAS) AF: 0.136 AC: 3492 AN: 25744

European-Finnish (FIN) AF: 0.109 AC: 1383 AN: 12632

Middle Eastern (MID) AF: 0.0370 AC: 50 AN: 1350

European-Non Finnish (NFE) AF: 0.0173 AC: 7830 AN: 451776

Other (OTH) AF: 0.0308 AC: 632 AN: 20496

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.144 AC: 1226 AN: 8526 Hom.: 0 Cov.: 0 AF XY: 0.147 AC XY: 605 AN XY: 4104

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

African (AFR) AF: 0.166 AC: 352 AN: 2124

American (AMR) AF: 0.173 AC: 168 AN: 970

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 30 AN: 190

East Asian (EAS) AF: 0.0918 AC: 18 AN: 196

South Asian (SAS) AF: 0.0354 AC: 8 AN: 226

European-Finnish (FIN) AF: 0.137 AC: 82 AN: 600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.135 AC: 546 AN: 4052

Other (OTH) AF: 0.148 AC: 18 AN: 122

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0787 Hom.: 0

ExAC AF: 0.0123 AC: 179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.7
DANN	Benign	0.38
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.065
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.028
Sift	Benign	0.27	T
Sift4G	Benign	0.35	T
Polyphen		0.0010	B
Vest4		0.069
MPC		0.43
ClinPred		0.0067	T
GERP RS		-2.6
Varity_R		0.16
gMVP		0.10
Mutation Taster		=95/5	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;