chr3-112580649-C-A

Variant names:

• chr3-112580649-C-A
• rs144280370
• NM_017945.5:c.532C>A

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.532C>A​(p.Arg178Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R178C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC35A5 NM_017945.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.62
• Publications: 1 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=0.15993932).

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.532C>A	p.Arg178Ser	missense	Exon 6 of 7	NP_060415.1	Q9BS91
	SLC35A5	NM_001348905.2		c.532C>A	p.Arg178Ser	missense	Exon 6 of 7	NP_001335834.1	Q9BS91
	SLC35A5	NM_001348906.2		c.532C>A	p.Arg178Ser	missense	Exon 6 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.532C>A	p.Arg178Ser	missense	Exon 6 of 7	ENSP00000417654.1	Q9BS91
	SLC35A5	ENST00000890627.1		c.532C>A	p.Arg178Ser	missense	Exon 6 of 8	ENSP00000560686.1
	SLC35A5	ENST00000890628.1		c.532C>A	p.Arg178Ser	missense	Exon 5 of 6	ENSP00000560687.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.19
Eigen_PC	Benign	0.039
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
PhyloP100		3.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.14	N
REVEL	Benign	0.085
Sift	Benign	0.22	T
Sift4G	Benign	0.49	T
Polyphen		0.0020	B
Vest4		0.27
MutPred		0.53		Gain of glycosylation at R178 (P = 0.003)
MVP		0.57
MPC		0.17
ClinPred		0.67	D
GERP RS		5.8
Varity_R		0.28
gMVP		0.39
Mutation Taster		=87/13	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: rs144280370; hg19: chr3-112299496; COSMIC: COSV53727041;