Variant rs17014118 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017912.4(HERC6):c.1027T>A(p.Phe343Ile) variant causes a missense, splice region 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. 16/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. F343L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HERC6
NM_017912.4 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.330

Variant links:

Genes affected

HERC6 (HGNC:26072): (HECT and RLD domain containing E3 ubiquitin protein ligase family member 6) HERC6 belongs to the HERC family of ubiquitin ligases, all of which contain a HECT domain and at least 1 RCC1 (MIM 179710)-like domain (RLD). The 350-amino acid HECT domain is predicted to catalyze the formation of a thioester with ubiquitin before transferring it to a substrate, and the RLD is predicted to act as a guanine nucleotide exchange factor for small G proteins (Hochrainer et al., 2005 [PubMed 15676274]).[supplied by OMIM, Mar 2008]

HERC6 links:

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ACMG classification

Classification made for transcript

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=0.09239739).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HERC6	NM_017912.4 linkuse as main transcript	c.1027T>A	p.Phe343Ile	missense_variant, splice_region_variant	8/23	ENST00000264346.12	NP_060382.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HERC6	ENST00000264346.12 linkuse as main transcript	c.1027T>A	p.Phe343Ile	missense_variant, splice_region_variant	8/23	1	NM_017912.4	ENSP00000264346	P1	Q8IVU3-1
HERC6	ENST00000380265.9 linkuse as main transcript	c.1027T>A	p.Phe343Ile	missense_variant, splice_region_variant	8/22	1		ENSP00000369617		Q8IVU3-2
HERC6	ENST00000506714.5 linkuse as main transcript	n.855T>A		non_coding_transcript_exon_variant	7/8	2
HERC6	ENST00000515365.1 linkuse as main transcript	n.423T>A		splice_region_variant, non_coding_transcript_exon_variant	5/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1430640

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

710168

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0018

.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.52

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.092

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.31

PROVEAN

Benign

0.11

N;N

REVEL

Benign

0.094

Sift

Benign

0.16

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.038

B;B

Vest4

0.25

MutPred

0.50

Loss of catalytic residue at F343 (P = 0.0384);Loss of catalytic residue at F343 (P = 0.0384);

MVP

0.81

MPC

0.21

ClinPred

0.095

GERP RS

2.6

Varity_R

0.057

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over