rs560277073

Variant names:

• chr7-29884045-C-T
• rs560277073
• NM_001080529.3:c.551C>T

Variant summary

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

The NM_001080529.3(WIPF3):​c.551C>T​(p.Pro184Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,426,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.037021667).

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.551C>T	p.Pro184Leu	missense	Exon 5 of 9	NP_001073998.2	A6NGB9
	WIPF3	NM_001391973.1		c.551C>T	p.Pro184Leu	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.551C>T	p.Pro184Leu	missense	Exon 5 of 9	ENSP00000242140.6	A6NGB9
	WIPF3	ENST00000409123.5	TSL:5	c.551C>T	p.Pro184Leu	missense	Exon 5 of 8	ENSP00000386790.1	A0A0A0MSG0
	WIPF3	ENST00000869766.1		c.551C>T	p.Pro184Leu	missense	Exon 5 of 9	ENSP00000539825.1

Frequencies

GnomAD3 genomes AF: 0.000312 AC: 45 AN: 144008 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000274

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000986

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000492

Gnomad OTH AF: 0.00102

GnomAD2 exomes AF: 0.000300 AC: 28 AN: 93440 AF XY: 0.000227

Gnomad AFR exome AF: 0.000197

Gnomad AMR exome AF: 0.000155

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000786

Gnomad OTH exome AF: 0.000365

GnomAD4 exome AF: 0.000646 AC: 828 AN: 1282022 Hom.: 0 Cov.: 22 AF XY: 0.000662 AC XY: 414 AN XY: 625564

African (AFR) AF: 0.000106 AC: 3 AN: 28436

American (AMR) AF: 0.000137 AC: 4 AN: 29146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20838

East Asian (EAS) AF: 0.00 AC: 0 AN: 32026

South Asian (SAS) AF: 0.00 AC: 0 AN: 66406

European-Finnish (FIN) AF: 0.0000907 AC: 4 AN: 44102

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3680

European-Non Finnish (NFE) AF: 0.000794 AC: 797 AN: 1004178

Other (OTH) AF: 0.000376 AC: 20 AN: 53210

GnomAD4 genome AF: 0.000312 AC: 45 AN: 144106 Hom.: 0 Cov.: 21 AF XY: 0.000285 AC XY: 20 AN XY: 70126

African (AFR) AF: 0.000154 AC: 6 AN: 38934

American (AMR) AF: 0.000273 AC: 4 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3328

East Asian (EAS) AF: 0.00 AC: 0 AN: 4678

South Asian (SAS) AF: 0.00 AC: 0 AN: 4258

European-Finnish (FIN) AF: 0.0000986 AC: 1 AN: 10142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.000492 AC: 32 AN: 64994

Other (OTH) AF: 0.00101 AC: 2 AN: 1974

Alfa AF: 0.0000693 Hom.: 0

ExAC AF: 0.000200 AC: 4

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	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	0.00011
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.58	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0080	D
Polyphen		1.0	D
Vest4		0.24
MVP		0.36
MPC		0.41
ClinPred		0.064	T
GERP RS		2.4
Varity_R		0.098
gMVP		0.22
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: rs560277073; hg19: chr7-29923661;