20-46350456-T-G

Variant names:

• chr20-46350456-T-G
• rs2059164951
• NM_015945.12:c.1036A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015945.12(SLC35H1):​c.1036A>C​(p.Ser346Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC35H1 NM_015945.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.322
• Publications: 0 publications found

Genes affected

SLC35H1 (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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057845116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015945.12. 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
	SLC35H1	NM_015945.12	MANE Select	c.1036A>C	p.Ser346Arg	missense	Exon 10 of 10	NP_057029.8
	SLC35H1	NM_001281458.2		c.1123A>C	p.Ser375Arg	missense	Exon 11 of 11	NP_001268387.1	Q9NQQ7-3
	SLC35H1	NM_001281460.2		c.1036A>C	p.Ser346Arg	missense	Exon 11 of 11	NP_001268389.1	Q9NQQ7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35C2	ENST00000372230.10	TSL:1 MANE Select	c.1036A>C	p.Ser346Arg	missense	Exon 10 of 10	ENSP00000361304.5	Q9NQQ7-1
	SLC35C2	ENST00000243896.6	TSL:1	c.1036A>C	p.Ser346Arg	missense	Exon 10 of 10	ENSP00000243896.2	Q9NQQ7-1
	SLC35C2	ENST00000372227.5	TSL:1	c.1036A>C	p.Ser346Arg	missense	Exon 10 of 10	ENSP00000361301.1	Q9NQQ7-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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	0.15
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.67	N
PhyloP100		-0.32
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.070
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.074	T
Polyphen		0.0	B
Vest4		0.080
MutPred		0.26		Loss of phosphorylation at S375 (P = 0.0013)
MVP		0.32
MPC		0.36
ClinPred		0.89	D
GERP RS		1.1
Varity_R		0.083
gMVP		0.38
Mutation Taster		=84/16	polymorphism

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: rs2059164951; hg19: chr20-44979095;