rs773464165

Variant names:

• chr20-46354948-C-A
• NM_015945.12:c.595G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-46354948-C-A
• chr20-46354948-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_015945.12(SLC35C2):​c.595G>T​(p.Asp199Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,594 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: 6.8e-7 (0 hom.)
• Consequence: SLC35C2 NM_015945.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.50

Genes affected

SLC35C2 (HGNC:17117): (solute carrier family 35 member C2) This gene encodes a member of the triose-phosphate transporter protein family. This gene is regulated by oxygen tension, is induced in hypoxic trophoblast cells, and is overexpressed in ovarian cancer. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on the X chromosome. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35C2	NM_015945.12	c.595G>T	p.Asp199Tyr	missense_variant	Exon 7 of 10	ENST00000372230.10	NP_057029.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35C2	ENST00000372230.10	c.595G>T	p.Asp199Tyr	missense_variant	Exon 7 of 10	1	NM_015945.12	ENSP00000361304.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461594 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727086

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: 0.0000116

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	0.98
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	.;T;T;T;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;.;.;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.95	D;D;D;D;D
MetaSVM	Uncertain	0.036	D
MutationAssessor	Uncertain	2.6	.;M;M;M;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Pathogenic	-8.4	.;D;D;D;.
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0010	.;D;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		1.0	D;D;D;D;.
Vest4		0.85
MutPred		0.81		.;.;.;.;Gain of catalytic residue at I227 (P = 0.0547);
MVP		0.84
MPC		1.2
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.94
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr20-44983587;