7-43438102-C-G

Position:

• chr7-43438102-C-G

Variant summary

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

The ENST00000395891.7(HECW1):​c.901C>G​(p.Leu301Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: HECW1 ENST00000395891.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.32

Genes affected

HECW1 (HGNC:22195): (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including cellular protein metabolic process; negative regulation of sodium ion transmembrane transporter activity; and regulation of dendrite morphogenesis. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HECW1	NM_015052.5	c.901C>G	p.Leu301Val	missense_variant	9/30	ENST00000395891.7	NP_055867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HECW1	ENST00000395891.7	c.901C>G	p.Leu301Val	missense_variant	9/30	1	NM_015052.5	ENSP00000379228	P2
HECW1	ENST00000453890.5	c.901C>G	p.Leu301Val	missense_variant	8/28	2		ENSP00000407774	A2
HECW1	ENST00000471043.1	n.393C>G		non_coding_transcript_exon_variant	4/4	2
HECW1	ENST00000492310.5	n.1525C>G		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Nov 22, 2023

The c.901C>G (p.L301V) alteration is located in exon 9 (coding exon 7) of the HECW1 gene. This alteration results from a C to G substitution at nucleotide position 901, causing the leucine (L) at amino acid position 301 to be replaced by a valine (V). 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	Uncertain	0.49
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Uncertain	-0.040	T
MutationAssessor	Uncertain	2.7	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.8	N;N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.69
MutPred		0.49		Gain of methylation at K300 (P = 0.0321);Gain of methylation at K300 (P = 0.0321);
MVP		0.52
MPC		1.4
ClinPred		0.94	D
GERP RS		4.4
Varity_R		0.39
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr7-43477701;