7-123709101-T-C

Variant names:

• chr7-123709101-T-C
• rs1187911050
• NM_003941.4:c.240A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003941.4(WASL):​c.240A>G​(p.Ile80Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000358 in 1,453,006 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: WASL NM_003941.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 52 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003941.4. 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
	WASL	NM_003941.4	MANE Select	c.240A>G	p.Ile80Met	missense	Exon 2 of 11	NP_003932.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WASL	ENST00000223023.5	TSL:1 MANE Select	c.240A>G	p.Ile80Met	missense	Exon 2 of 11	ENSP00000223023.4	O00401
	WASL	ENST00000924343.1		c.240A>G	p.Ile80Met	missense	Exon 2 of 11	ENSP00000594402.1
	WASL	ENST00000924344.1		c.240A>G	p.Ile80Met	missense	Exon 2 of 10	ENSP00000594403.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000358 AC: 52 AN: 1453006 Hom.: 0 Cov.: 30 AF XY: 0.0000291 AC XY: 21 AN XY: 722426

African (AFR) AF: 0.00 AC: 0 AN: 33224

American (AMR) AF: 0.00 AC: 0 AN: 43674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25842

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.00 AC: 0 AN: 83938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53110

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.0000469 AC: 52 AN: 1107998

Other (OTH) AF: 0.00 AC: 0 AN: 59968

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.31
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	-0.11
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D
M_CAP	Pathogenic	0.29	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Pathogenic	0.94	D
MutationAssessor	Benign	0.28	N
PhyloP100		1.6
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.90	N
REVEL	Uncertain	0.60
Sift	Benign	0.096	T
Sift4G	Benign	0.15	T
Polyphen		0.085	B
Vest4		0.54
MutPred		0.55		Loss of ubiquitination at K84 (P = 0.0768)
MVP		0.71
MPC		0.43
ClinPred		0.45	T
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.55
Mutation Taster		=79/21	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: rs1187911050; hg19: chr7-123349155;