chr7-44201154-A-C

Variant names:

• chr7-44201154-A-C
• NM_006555.4:c.19A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006555.4(YKT6):​c.19A>C​(p.Ser7Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,456,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: YKT6 NM_006555.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.49

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YKT6	NM_006555.4	c.19A>C	p.Ser7Arg	missense_variant	Exon 1 of 7	ENST00000223369.3	NP_006546.1
YKT6	NM_001410874.1	c.19A>C	p.Ser7Arg	missense_variant	Exon 1 of 8		NP_001397803.1
YKT6	NM_001363678.2	c.19A>C	p.Ser7Arg	missense_variant	Exon 1 of 6		NP_001350607.1
YKT6	XM_054328423.1	c.19A>C	p.Ser7Arg	missense_variant	Exon 1 of 7		XP_054184398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YKT6	ENST00000223369.3	c.19A>C	p.Ser7Arg	missense_variant	Exon 1 of 7	1	NM_006555.4	ENSP00000223369.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1456876 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724488

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	.;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.78	D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.26
Sift	Benign	0.030	D;T
Sift4G	Benign	0.43	T;T
Polyphen		1.0	.;D
Vest4		0.87
MutPred		0.53		Gain of MoRF binding (P = 6e-04);Gain of MoRF binding (P = 6e-04);
MVP		0.068
MPC		1.1
ClinPred		0.98	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.86
gMVP		0.81

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: chr7-44240753;