3-112573922-A-T

Variant names:

• chr3-112573922-A-T
• rs142275743
• NM_017945.5:c.394A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017945.5(SLC35A5):​c.394A>T​(p.Ile132Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000164 in 1,613,560 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: SLC35A5 NM_017945.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23182425).

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.394A>T	p.Ile132Leu	missense	Exon 5 of 7	NP_060415.1	Q9BS91
	SLC35A5	NM_001348905.2		c.394A>T	p.Ile132Leu	missense	Exon 5 of 7	NP_001335834.1	Q9BS91
	SLC35A5	NM_001348906.2		c.394A>T	p.Ile132Leu	missense	Exon 5 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.394A>T	p.Ile132Leu	missense	Exon 5 of 7	ENSP00000417654.1	Q9BS91
	SLC35A5	ENST00000890627.1		c.394A>T	p.Ile132Leu	missense	Exon 5 of 8	ENSP00000560686.1
	SLC35A5	ENST00000890628.1		c.394A>T	p.Ile132Leu	missense	Exon 4 of 6	ENSP00000560687.1

Frequencies

GnomAD3 genomes AF: 0.000190 AC: 29 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000115 AC: 29 AN: 251318 AF XY: 0.000155

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000161 AC: 236 AN: 1461318 Hom.: 1 Cov.: 29 AF XY: 0.000186 AC XY: 135 AN XY: 726990

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.000134 AC: 6 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5764

European-Non Finnish (NFE) AF: 0.000191 AC: 212 AN: 1111596

Other (OTH) AF: 0.000215 AC: 13 AN: 60370

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74378

African (AFR) AF: 0.0000724 AC: 3 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68052

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.000204

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000273

EpiControl AF: 0.000296

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	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.050
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.96	L
PhyloP100		4.1
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.20
Sift	Benign	0.24	T
Sift4G	Benign	0.28	T
Polyphen		0.15	B
Vest4		0.42
MutPred		0.68		Loss of catalytic residue at L137 (P = 0.0336)
MVP		0.61
MPC		0.24
ClinPred		0.10	T
GERP RS		5.9
Varity_R		0.17
gMVP		0.54
Mutation Taster		=71/29	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: rs142275743; hg19: chr3-112292769;