NM_001375834.1:c.1037C>G

Variant names:

• chr2-174571768-G-C
• NM_001375834.1:c.1037C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001375834.1(WIPF1):​c.1037C>G​(p.Pro346Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WIPF1 NM_001375834.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.90

Genes affected

WIPF1 (HGNC:12736): (WAS/WASL interacting protein family member 1) This gene encodes a protein that plays an important role in the organization of the actin cytoskeleton. The encoded protein binds to a region of Wiskott-Aldrich syndrome protein that is frequently mutated in Wiskott-Aldrich syndrome, an X-linked recessive disorder. Impairment of the interaction between these two proteins may contribute to the disease. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ENSG00000236449 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3423814).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF1	NM_001375834.1	c.1037C>G	p.Pro346Arg	missense_variant	Exon 5 of 8	ENST00000679041.1	NP_001362763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000679041.1	c.1037C>G	p.Pro346Arg	missense_variant	Exon 5 of 8		NM_001375834.1	ENSP00000503603.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461894 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.62	D;.;D;D;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	.;T;.;T;T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.34	T;T;T;T;T;T
MetaSVM	Benign	-0.39	T
MutationAssessor	Uncertain	2.6	M;M;M;M;M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.9	D;D;D;D;N;D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;D;D;D;D
Sift4G	Benign	0.094	T;T;T;T;T;D
Polyphen		1.0	D;D;D;D;D;D
Vest4		0.41
MutPred		0.31		Gain of MoRF binding (P = 0.0017);Gain of MoRF binding (P = 0.0017);Gain of MoRF binding (P = 0.0017);Gain of MoRF binding (P = 0.0017);Gain of MoRF binding (P = 0.0017);Gain of MoRF binding (P = 0.0017);
MVP		0.29
MPC		0.48
ClinPred		0.93	D
GERP RS		5.0
Varity_R		0.14
gMVP		0.27

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-175436496;