rs1808593738

Variant names:

• chr7-43312027-A-C
• rs1808593738
• NM_015052.5:c.292A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-43312027-A-C
• chr7-43312027-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015052.5(HECW1):​c.292A>C​(p.Ile98Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I98V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: HECW1 NM_015052.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.17
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28339952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HECW1	NM_015052.5	c.292A>C	p.Ile98Leu	missense_variant	Exon 4 of 30	ENST00000395891.7	NP_055867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HECW1	ENST00000395891.7	c.292A>C	p.Ile98Leu	missense_variant	Exon 4 of 30	1	NM_015052.5	ENSP00000379228.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.097	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L
PhyloP100		4.2
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.079
Sift	Benign	0.052	T;T
Sift4G	Uncertain	0.051	T;D
Polyphen		0.39	B;.
Vest4		0.68
MutPred		0.26		Gain of catalytic residue at I98 (P = 0.011);Gain of catalytic residue at I98 (P = 0.011);
MVP		0.14
MPC		0.93
ClinPred		0.83	D
GERP RS		6.1
Varity_R		0.19
gMVP		0.70
Mutation Taster		=95/5	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: rs1808593738; hg19: chr7-43351626;