rs1290480775

Variant names:

• chr7-29883879-C-A
• rs1290480775
• NM_001080529.3:c.385C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-29883879-C-A
• chr7-29883879-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001080529.3(WIPF3):​c.385C>A​(p.Arg129Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,678 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. 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. R129G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.946
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28868657).

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.385C>A	p.Arg129Ser	missense	Exon 5 of 9	NP_001073998.2	A6NGB9
	WIPF3	NM_001391973.1		c.385C>A	p.Arg129Ser	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.385C>A	p.Arg129Ser	missense	Exon 5 of 9	ENSP00000242140.6	A6NGB9
	WIPF3	ENST00000409123.5	TSL:5	c.385C>A	p.Arg129Ser	missense	Exon 5 of 8	ENSP00000386790.1	A0A0A0MSG0
	WIPF3	ENST00000869766.1		c.385C>A	p.Arg129Ser	missense	Exon 5 of 9	ENSP00000539825.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416678 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 698390

African (AFR) AF: 0.00 AC: 0 AN: 32664

American (AMR) AF: 0.00 AC: 0 AN: 41694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23280

East Asian (EAS) AF: 0.00 AC: 0 AN: 39140

South Asian (SAS) AF: 0.00 AC: 0 AN: 79204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1085920

Other (OTH) AF: 0.00 AC: 0 AN: 58346

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.95
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.25		Gain of phosphorylation at R129 (P = 0.0142)
MVP		0.54
MPC		0.15
ClinPred		0.62	D
GERP RS		1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.28
gMVP		0.40
Mutation Taster		=89/11	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: rs1290480775; hg19: chr7-29923495;