NM_017945.5:c.50T>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 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)
  • 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017945.5. 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
	SLC35A5	NM_017945.5	MANE Select	c.50T>C	p.Met17Thr	missense	Exon 2 of 7	NP_060415.1	Q9BS91
	SLC35A5	NM_001348905.2		c.50T>C	p.Met17Thr	missense	Exon 2 of 7	NP_001335834.1	Q9BS91
	SLC35A5	NM_001348906.2		c.50T>C	p.Met17Thr	missense	Exon 2 of 7	NP_001335835.1	Q9BS91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35A5	ENST00000492406.6	TSL:1 MANE Select	c.50T>C	p.Met17Thr	missense	Exon 2 of 7	ENSP00000417654.1	Q9BS91
	SLC35A5	ENST00000890627.1		c.50T>C	p.Met17Thr	missense	Exon 2 of 8	ENSP00000560686.1
	SLC35A5	ENST00000890628.1		c.50T>C	p.Met17Thr	missense	Exon 1 of 6	ENSP00000560687.1

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

African (AFR) AF: 0.0000300 AC: 1 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25788

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.00 AC: 0 AN: 85350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5708

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102706

Other (OTH) AF: 0.00 AC: 0 AN: 59764

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	0.067
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
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.39
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.048
Sift	Benign	0.069	T
Sift4G	Benign	0.12	T
Polyphen		0.017	B
Vest4		0.30
MutPred		0.59		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
Mutation Taster		=86/14	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: rs1934036535; hg19: chr3-112282300;