Variant 17-81693579-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004712.5(HGS):c.739C>G(p.Gln247Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000842 in 1,602,920 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00094 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00083 ( 2 hom. )

Consequence

HGS
NM_004712.5 missense, splice_region

Scores

Splicing: ADA: 0.6786

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.21

Variant links:

Genes affected

HGS (HGNC:4897): (hepatocyte growth factor-regulated tyrosine kinase substrate) The protein encoded by this gene regulates endosomal sorting and plays a critical role in the recycling and degradation of membrane receptors. The encoded protein sorts monoubiquitinated membrane proteins into the multivesicular body, targeting these proteins for lysosome-dependent degradation. [provided by RefSeq, Dec 2010]

HGS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013174534).

BP6

Variant 17-81693579-C-G is Benign according to our data. Variant chr17-81693579-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 725635.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HGS	NM_004712.5 linkuse as main transcript	c.739C>G	p.Gln247Glu	missense_variant, splice_region_variant	9/22	ENST00000329138.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HGS	ENST00000329138.9 linkuse as main transcript	c.739C>G	p.Gln247Glu	missense_variant, splice_region_variant	9/22	1	NM_004712.5	P1	O14964-1

Frequencies

GnomAD3 genomes

AF:

0.000941

AC:

143

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00104

AC:

255

AN:

244626

Hom.:

AF XY:

0.00107

AC XY:

142

AN XY:

132410

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000402

Gnomad FIN exome

AF:

0.000283

Gnomad NFE exome

AF:

0.00127

Gnomad OTH exome

AF:

0.00218

GnomAD4 exome

AF:

0.000832

AC:

1207

AN:

1450788

Hom.:

Cov.:

AF XY:

0.000828

AC XY:

597

AN XY:

721320

show subpopulations

Gnomad4 AFR exome

AF:

0.000240

Gnomad4 AMR exome

AF:

0.00176

Gnomad4 ASJ exome

AF:

0.00214

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000468

Gnomad4 FIN exome

AF:

0.000265

Gnomad4 NFE exome

AF:

0.000850

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000940

AC:

143

AN:

152132

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00341

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000861

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000833

AC:

101

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.45

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.11

Sift

Uncertain

0.016

D;.

Sift4G

Benign

0.16

T;T

Polyphen

0.58

P;.

Vest4

0.62

MVP

0.86

MPC

0.0099

ClinPred

0.095

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

3.8

Varity_R

0.25

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.68

dbscSNV1_RF

Benign

0.58

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over