chr7-44206388-A-G

Variant names:

• chr7-44206388-A-G
• rs138273846
• NM_006555.4:c.191A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.85
• Publications: 7 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 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

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.191A>G	p.Tyr64Cys	missense	Exon 3 of 7	NP_006546.1	A4D2J0
	YKT6	NM_001410874.1		c.191A>G	p.Tyr64Cys	missense	Exon 3 of 8	NP_001397803.1	A0A7I2V4L6
	YKT6	NM_001363678.2		c.191A>G	p.Tyr64Cys	missense	Exon 3 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.191A>G	p.Tyr64Cys	missense	Exon 3 of 7	ENSP00000223369.2	O15498-1
	YKT6	ENST00000677090.1		c.191A>G	p.Tyr64Cys	missense	Exon 3 of 8	ENSP00000504160.1	A0A7I2V4L6
	YKT6	ENST00000678359.1		c.191A>G	p.Tyr64Cys	missense	Exon 3 of 8	ENSP00000503337.1	A0A7I2V4L6

Frequencies

GnomAD3 genomes AF: 0.000683 AC: 104 AN: 152174 Hom.: 0 Cov.: 32

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

GnomAD2 exomes AF: 0.000533 AC: 134 AN: 251424 AF XY: 0.000375

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 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.: 0 Cov.: 31 AF XY: 0.000562 AC XY: 409 AN XY: 727178

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.000626 AC: 28 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000918 AC: 24 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53414

Middle Eastern (MID) AF: 0.000352 AC: 2 AN: 5680

European-Non Finnish (NFE) AF: 0.000710 AC: 789 AN: 1111966

Other (OTH) AF: 0.000497 AC: 30 AN: 60384

GnomAD4 genome AF: 0.000683 AC: 104 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.000592 AC XY: 44 AN XY: 74354

African (AFR) AF: 0.000193 AC: 8 AN: 41424

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00132 AC: 90 AN: 68034

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000918 Hom.: 0

Bravo AF: 0.000665

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00104 AC: 4

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00128 AC: 11

ExAC AF: 0.000404 AC: 49

EpiCase AF: 0.00125

EpiControl AF: 0.000711

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	Pathogenic	0.59
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		8.8
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.96
MVP		0.41
MPC		1.1
ClinPred		0.28	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.71
gMVP		0.83
Mutation Taster		=12/88	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

dbSNP: rs138273846; hg19: chr7-44245987;