Variant chr7-44206388-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006555.4(YKT6):c.191A>G(p.Tyr64Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000608 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 0 hom. )

Consequence

YKT6
NM_006555.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.85

Variant links:

Genes affected

YKT6 (HGNC:16959): (YKT6 v-SNARE homolog) This gene product is one of the SNARE recognition molecules implicated in vesicular transport between secretory compartments. It is a membrane associated, isoprenylated protein that functions at the endoplasmic reticulum-Golgi transport step. This protein is highly conserved from yeast to human and can functionally complement the loss of the yeast homolog in the yeast secretory pathway. [provided by RefSeq, Jul 2008]

YKT6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
YKT6	NM_006555.4 linkuse as main transcript	c.191A>G	p.Tyr64Cys	missense_variant	3/7	ENST00000223369.3
YKT6	NM_001410874.1 linkuse as main transcript	c.191A>G	p.Tyr64Cys	missense_variant	3/8
YKT6	NM_001363678.2 linkuse as main transcript	c.191A>G	p.Tyr64Cys	missense_variant	3/6
YKT6	XM_054328423.1 linkuse as main transcript	c.191A>G	p.Tyr64Cys	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YKT6	ENST00000223369.3 linkuse as main transcript	c.191A>G	p.Tyr64Cys	missense_variant	3/7	1	NM_006555.4	P1	O15498-1

Frequencies

GnomAD3 genomes

AF:

0.000683

AC:

104

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000533

AC:

134

AN:

251424

Hom.:

AF XY:

0.000375

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000809

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000601

AC:

878

AN:

1461734

Hom.:

Cov.:

AF XY:

0.000562

AC XY:

409

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.000918

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000710

Gnomad4 OTH exome

AF:

0.000497

GnomAD4 genome

AF:

0.000683

AC:

104

AN:

152174

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00132

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000929

Hom.:

Bravo

AF:

0.000665

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000404

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.000711

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2021

The c.191A>G (p.Y64C) alteration is located in exon 3 (coding exon 3) of the YKT6 gene. This alteration results from a A to G substitution at nucleotide position 191, causing the tyrosine (Y) at amino acid position 64 to be replaced by a cysteine (C). 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

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Uncertain

0.11

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Benign

-0.41

MutationAssessor

Pathogenic

3.7

H;H

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-8.8

D;D

REVEL

Pathogenic

0.75

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

.;D

Vest4

0.96

MVP

0.41

MPC

1.1

ClinPred

0.28

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.71

gMVP

0.83

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over