Genetic Variant SLC29A2:p.Gly166Ser (chr11-66368591-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001532.3(SLC29A2):c.496G>A(p.Gly166Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SLC29A2
NM_001532.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.42

Publications

1 publications found

Variant links:

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]

SLC29A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.986

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC29A2	NM_001532.3	MANE Select	c.496G>A	p.Gly166Ser	missense	Exon 5 of 12	NP_001523.2
SLC29A2	NM_001300868.2		c.496G>A	p.Gly166Ser	missense	Exon 7 of 14	NP_001287797.1	Q14542-1
SLC29A2	NM_001300869.2		c.496G>A	p.Gly166Ser	missense	Exon 7 of 13	NP_001287798.1	Q14542-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC29A2	ENST00000357440.7	TSL:1 MANE Select	c.496G>A	p.Gly166Ser	missense	Exon 5 of 12	ENSP00000350024.2	Q14542-1
SLC29A2	ENST00000311161.11	TSL:1	c.496G>A	p.Gly166Ser	missense	Exon 6 of 12	ENSP00000311250.7	Q14542-4
SLC29A2	ENST00000540386.5	TSL:1	n.496G>A		non_coding_transcript_exon	Exon 5 of 12	ENSP00000444870.1	Q14542-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

242552

AF XY:

0.0000152

show subpopulations

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:

0.00000914

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000822

AC:

AN:

1458990

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725432

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26014

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.0000350

AC:

AN:

85646

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1110896

Other (OTH)

AF:

0.0000166

AC:

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.87

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.40

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.22

MetaRNN

Pathogenic

0.99

MetaSVM

Pathogenic

0.88

MutationAssessor

Pathogenic

3.7

PhyloP100

7.4

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-5.9

REVEL

Pathogenic

0.86

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.88

MutPred

0.97

Loss of glycosylation at S165 (P = 0.0325)

MVP

0.78

MPC

0.57

ClinPred

1.0

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.93

gMVP

0.86

Mutation Taster

=17/83

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.19

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over