7-29879028-A-T

Position:

• chr7-29879028-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080529.3(WIPF3):​c.243A>T​(p.Lys81Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,448,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: WIPF3 NM_001080529.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.20

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19793779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF3	NM_001080529.3	c.243A>T	p.Lys81Asn	missense_variant	4/9	ENST00000242140.10	NP_001073998.2
WIPF3	NM_001391973.1	c.243A>T	p.Lys81Asn	missense_variant	4/8		NP_001378902.1
WIPF3	XM_017012522.2	c.210A>T	p.Lys70Asn	missense_variant	3/8		XP_016868011.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPF3	ENST00000242140.10	c.243A>T	p.Lys81Asn	missense_variant	4/9	5	NM_001080529.3	ENSP00000242140.6
WIPF3	ENST00000409123.5	c.243A>T	p.Lys81Asn	missense_variant	4/8	5		ENSP00000386790.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1448546 Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8 AN XY: 718890

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: 0.0000154

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.243A>T (p.K81N) alteration is located in exon 4 (coding exon 3) of the WIPF3 gene. This alteration results from a A to T substitution at nucleotide position 243, causing the lysine (K) at amino acid position 81 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;T;T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.71	T;T;.
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	.;M;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.0	N;N;N
REVEL	Benign	0.081
Sift	Uncertain	0.026	D;D;D
Sift4G	Benign	0.21	T;T;T
Polyphen		0.99	.;D;D
Vest4		0.32
MutPred		0.12		Loss of ubiquitination at K81 (P = 0.0014);Loss of ubiquitination at K81 (P = 0.0014);Loss of ubiquitination at K81 (P = 0.0014);
MVP		0.30
MPC		0.45
ClinPred		0.90	D
GERP RS		1.9
Varity_R		0.17
gMVP		0.18

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: chr7-29918644;