NM_001532.3:c.533T>C

Variant names:

• chr11-66368554-A-G
• NM_001532.3:c.533T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001532.3(SLC29A2):​c.533T>C​(p.Met178Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC29A2 NM_001532.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.77
• Publications: 0 publications found

Genes affected

SLC29A2 (HGNC:11004): (solute carrier family 29 member 2) The uptake of nucleosides by transporters, such as SLC29A2, is essential for nucleotide synthesis by salvage pathways in cells that lack de novo biosynthetic pathways. Nucleoside transport also plays a key role in the regulation of many physiologic processes through its effect on adenosine concentration at the cell surface (Griffiths et al., 1997 [PubMed 9396714]).[supplied by OMIM, Nov 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.926

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001532.3. 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
	SLC29A2	NM_001532.3	MANE Select	c.533T>C	p.Met178Thr	missense	Exon 5 of 12	NP_001523.2
	SLC29A2	NM_001300868.2		c.533T>C	p.Met178Thr	missense	Exon 7 of 14	NP_001287797.1	Q14542-1
	SLC29A2	NM_001300869.2		c.533T>C	p.Met178Thr	missense	Exon 7 of 13	NP_001287798.1	Q14542-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A2	ENST00000357440.7	TSL:1 MANE Select	c.533T>C	p.Met178Thr	missense	Exon 5 of 12	ENSP00000350024.2	Q14542-1
	SLC29A2	ENST00000311161.11	TSL:1	c.533T>C	p.Met178Thr	missense	Exon 6 of 12	ENSP00000311250.7	Q14542-4
	SLC29A2	ENST00000540386.5	TSL:1	n.533T>C		non_coding_transcript_exon	Exon 5 of 12	ENSP00000444870.1	Q14542-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Uncertain	0.54
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.68
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	0.071	D
MutationAssessor	Benign	2.0	M
PhyloP100		8.8
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.70
Sift	Benign	0.24	T
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.85		Loss of stability (P = 0.0375)
MVP		0.66
MPC		0.61
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.61
Mutation Taster		=49/51	disease causing

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

hg19: chr11-66136025;