7-44204647-C-A

Position:

• chr7-44204647-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006555.4(YKT6):​c.184C>A​(p.Gln62Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: YKT6 NM_006555.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.49

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4036022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YKT6	NM_006555.4	c.184C>A	p.Gln62Lys	missense_variant	2/7	ENST00000223369.3	NP_006546.1
YKT6	NM_001410874.1	c.184C>A	p.Gln62Lys	missense_variant	2/8		NP_001397803.1
YKT6	NM_001363678.2	c.184C>A	p.Gln62Lys	missense_variant	2/6		NP_001350607.1
YKT6	XM_054328423.1	c.184C>A	p.Gln62Lys	missense_variant	2/7		XP_054184398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YKT6	ENST00000223369.3	c.184C>A	p.Gln62Lys	missense_variant	2/7	1	NM_006555.4	ENSP00000223369	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2023

The c.184C>A (p.Q62K) alteration is located in exon 2 (coding exon 2) of the YKT6 gene. This alteration results from a C to A substitution at nucleotide position 184, causing the glutamine (Q) at amino acid position 62 to be replaced by a lysine (K). 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	0.11
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.069	.;T
Eigen	Benign	0.023
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.11
Sift	Benign	0.36	T;T
Sift4G	Benign	0.60	T;T
Polyphen		0.026	.;B
Vest4		0.67
MutPred		0.49		Gain of methylation at Q62 (P = 0.0047);Gain of methylation at Q62 (P = 0.0047);
MVP		0.17
MPC		0.42
ClinPred		0.74	D
GERP RS		5.4
Varity_R		0.50
gMVP		0.63

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.

Other links and lift over

hg19: chr7-44244246;