chr3-112563453-T-C

Variant names:

• chr3-112563453-T-C
• rs1934036535
• NM_017945.5:c.50T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017945.5(SLC35A5):​c.50T>C​(p.Met17Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC35A5 NM_017945.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.392

Genes affected

SLC35A5 (HGNC:20792): (solute carrier family 35 member A5) This gene encodes a transmembrane protein which belongs to subfamily 35A of the solute carrier superfamily. The encoded protein is a nucleoside-sugar transporter. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1549452).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35A5	NM_017945.5	c.50T>C	p.Met17Thr	missense_variant	Exon 2 of 7	ENST00000492406.6	NP_060415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35A5	ENST00000492406.6	c.50T>C	p.Met17Thr	missense_variant	Exon 2 of 7	1	NM_017945.5	ENSP00000417654.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449714 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 720220

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.50T>C (p.M17T) alteration is located in exon 2 (coding exon 1) of the SLC35A5 gene. This alteration results from a T to C substitution at nucleotide position 50, causing the methionine (M) at amino acid position 17 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.0072	.;T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Benign	0.048
Sift	Benign	0.069	T;T;T;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.017	.;B;.;.
Vest4		0.30, 0.25
MutPred		0.59		Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);Loss of stability (P = 0.024);
MVP		0.42
MPC		0.18
ClinPred		0.16	T
GERP RS		4.6
Varity_R		0.14
gMVP		0.34

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

LitVar

Other links and lift over

dbSNP: rs1934036535; hg19: chr3-112282300;