NM_006555.4:c.184C>A

Variant names:

• chr7-44204647-C-A
• NM_006555.4:c.184C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006555.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YKT6	NM_006555.4	MANE Select	c.184C>A	p.Gln62Lys	missense	Exon 2 of 7	NP_006546.1	A4D2J0
	YKT6	NM_001410874.1		c.184C>A	p.Gln62Lys	missense	Exon 2 of 8	NP_001397803.1	A0A7I2V4L6
	YKT6	NM_001363678.2		c.184C>A	p.Gln62Lys	missense	Exon 2 of 6	NP_001350607.1	O15498-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YKT6	ENST00000223369.3	TSL:1 MANE Select	c.184C>A	p.Gln62Lys	missense	Exon 2 of 7	ENSP00000223369.2	O15498-1
	YKT6	ENST00000677090.1		c.184C>A	p.Gln62Lys	missense	Exon 2 of 8	ENSP00000504160.1	A0A7I2V4L6
	YKT6	ENST00000678359.1		c.184C>A	p.Gln62Lys	missense	Exon 2 of 8	ENSP00000503337.1	A0A7I2V4L6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Benign	0.36	T
Sift4G	Benign	0.60	T
Polyphen		0.026	B
Vest4		0.67
MutPred		0.49		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
Mutation Taster		=47/53	disease causing

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

Other links and lift over

hg19: chr7-44244246;