Variant 7-44204615-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006555.4(YKT6):c.152C>T(p.Ser51Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

YKT6
NM_006555.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.21

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:

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ACMG classification

Classification made for transcript

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
YKT6	NM_006555.4 linkuse as main transcript	c.152C>T	p.Ser51Leu	missense_variant	2/7	ENST00000223369.3	NP_006546.1
YKT6	NM_001410874.1 linkuse as main transcript	c.152C>T	p.Ser51Leu	missense_variant	2/8		NP_001397803.1
YKT6	NM_001363678.2 linkuse as main transcript	c.152C>T	p.Ser51Leu	missense_variant	2/6		NP_001350607.1
YKT6	XM_054328423.1 linkuse as main transcript	c.152C>T	p.Ser51Leu	missense_variant	2/7		XP_054184398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YKT6	ENST00000223369.3 linkuse as main transcript	c.152C>T	p.Ser51Leu	missense_variant	2/7	1	NM_006555.4	ENSP00000223369	P1	O15498-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727240

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 10, 2023

The c.152C>T (p.S51L) alteration is located in exon 2 (coding exon 2) of the YKT6 gene. This alteration results from a C to T substitution at nucleotide position 152, causing the serine (S) at amino acid position 51 to be replaced by a leucine (L). 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

Benign

0.28

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

.;T

Eigen

Uncertain

0.67

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.57

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.7

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.2

D;D

REVEL

Benign

0.27

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

0.96

.;D

Vest4

0.62

MutPred

0.39

Loss of disorder (P = 0.0099);Loss of disorder (P = 0.0099);

MVP

0.12

MPC

0.62

ClinPred

0.99

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.64

gMVP

0.54

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over