7-29884026-A-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080529.3(WIPF3):​c.532A>G​(p.Thr178Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 549,470 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. 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06987539).

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>G	p.Thr178Ala	missense	Exon 5 of 9	NP_001073998.2	A6NGB9
	WIPF3	NM_001391973.1		c.532A>G	p.Thr178Ala	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>G	p.Thr178Ala	missense	Exon 5 of 9	ENSP00000242140.6	A6NGB9
	WIPF3	ENST00000409123.5	TSL:5	c.532A>G	p.Thr178Ala	missense	Exon 5 of 8	ENSP00000386790.1	A0A0A0MSG0
	WIPF3	ENST00000869766.1		c.532A>G	p.Thr178Ala	missense	Exon 5 of 9	ENSP00000539825.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000182 AC: 1 AN: 549470 Hom.: 0 Cov.: 22 AF XY: 0.00000377 AC XY: 1 AN XY: 265506

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: 28304

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: 0.00000219 AC: 1 AN: 456560

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

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.0
DANN	Benign	0.31
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.065
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.033
Sift	Benign	0.18	T
Sift4G	Benign	0.91	T
Polyphen		0.075	B
Vest4		0.13
MutPred		0.34		Loss of phosphorylation at T178 (P = 2e-04)
MVP		0.030
MPC		0.28
ClinPred		0.065	T
GERP RS		-2.6
Varity_R		0.087
gMVP		0.15
Mutation Taster		=96/4	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;