7-123748721-T-G

Position:

• chr7-123748721-T-G

Variant summary

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

The NM_003941.4(WASL):​c.14A>C​(p.Gln5Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: WASL NM_003941.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.478

Genes affected

WASL (HGNC:12735): (WASP like actin nucleation promoting factor) This gene encodes a member of the Wiskott-Aldrich syndrome (WAS) protein family. Wiskott-Aldrich syndrome proteins share similar domain structure, and associate with a variety of signaling molecules to alter the actin cytoskeleton. The encoded protein is highly expressed in neural tissues, and interacts with several proteins involved in cytoskeletal organization, including cell division control protein 42 (CDC42) and the actin-related protein-2/3 (ARP2/3) complex. The encoded protein may be involved in the formation of long actin microspikes, and in neurite extension. [provided by RefSeq, Jul 2013]

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=0.20113274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WASL	NM_003941.4	c.14A>C	p.Gln5Pro	missense_variant	1/11	ENST00000223023.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WASL	ENST00000223023.5	c.14A>C	p.Gln5Pro	missense_variant	1/11	1	NM_003941.4	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

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

Apr 07, 2023

The c.14A>C (p.Q5P) alteration is located in exon 1 (coding exon 1) of the WASL gene. This alteration results from a A to C substitution at nucleotide position 14, causing the glutamine (Q) at amino acid position 5 to be replaced by a proline (P). 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	Benign	0.051
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.43	T
M_CAP	Pathogenic	0.91	D
MetaRNN	Benign	0.20	T
MetaSVM	Pathogenic	1.3	D
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	0.58	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.030	N
REVEL	Uncertain	0.41
Sift	Benign	0.068	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.097		Gain of glycosylation at Q5 (P = 0.0314);
MVP		0.32
MPC		0.52
ClinPred		0.41	T
GERP RS		3.5
Varity_R		0.20
gMVP		0.46

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: chr7-123388775;