Genetic Variant SLC29A1:c.-52+8C>T (chr6-44223649-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001372327.1(SLC29A1):c.-52+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,202,240 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 8 hom. )

Consequence

SLC29A1
NM_001372327.1 splice_region, intron

Scores

Splicing: ADA: 0.00007013

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.920

Publications

0 publications found

Variant links:

Genes affected

SLC29A1 (HGNC:11003): (solute carrier family 29 member 1 (Augustine blood group)) This gene is a member of the equilibrative nucleoside transporter family. The gene encodes a transmembrane glycoprotein that localizes to the plasma and mitochondrial membranes and mediates the cellular uptake of nucleosides from the surrounding medium. The protein is categorized as an equilibrative (as opposed to concentrative) transporter that is sensitive to inhibition by nitrobenzylthioinosine (NBMPR). Nucleoside transporters are required for nucleotide synthesis in cells that lack de novo nucleoside synthesis pathways, and are also necessary for the uptake of cytotoxic nucleosides used for cancer and viral chemotherapies. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

SLC29A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 6-44223649-C-T is Benign according to our data. Variant chr6-44223649-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3040920.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 401 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372327.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC29A1	NM_001372327.1	MANE Select	c.-52+8C>T	splice_region intron	N/A	NP_001359256.1	Q99808-1
SLC29A1	NM_001078177.2		c.-468C>T	5_prime_UTR	Exon 1 of 14	NP_001071645.1	Q99808-1
SLC29A1	NM_001304462.2		c.186+1964C>T	intron	N/A	NP_001291391.1	Q99808-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC29A1	ENST00000371755.9	TSL:1 MANE Select	c.-52+8C>T	splice_region intron	N/A	ENSP00000360820.3	Q99808-1
SLC29A1	ENST00000393844.7	TSL:1	c.-51-3614C>T	intron	N/A	ENSP00000377427.1	Q99808-1
SLC29A1	ENST00000371740.10	TSL:1	c.-159+8C>T	splice_region intron	N/A	ENSP00000360805.6	A0A2U3TZJ7

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

400

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00500

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00230

AC:

165

AN:

71726

AF XY:

0.00218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000353

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00136

Gnomad NFE exome

AF:

0.00572

Gnomad OTH exome

AF:

0.00243

GnomAD4 exome

AF:

0.00438

AC:

4599

AN:

1050122

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

2186

AN XY:

513522

show subpopulations

African (AFR)

AF:

0.000612

AC:

AN:

19614

American (AMR)

AF:

0.000168

AC:

AN:

17828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13686

East Asian (EAS)

AF:

0.00

AC:

AN:

5030

South Asian (SAS)

AF:

0.0000907

AC:

AN:

66118

European-Finnish (FIN)

AF:

0.00257

AC:

AN:

11264

Middle Eastern (MID)

AF:

0.000750

AC:

AN:

2666

European-Non Finnish (NFE)

AF:

0.00509

AC:

4461

AN:

876640

Other (OTH)

AF:

0.00231

AC:

AN:

37276

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

222

444

667

889

1111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

216

432

648

864

1080

<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:

0.00264

AC:

401

AN:

152118

Hom.:

Cov.:

AF XY:

0.00198

AC XY:

147

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.000819

AC:

AN:

41536

American (AMR)

AF:

0.000392

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00151

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00502

AC:

341

AN:

67938

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00376

Hom.:

Bravo

AF:

0.00250

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

SLC29A1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.1

(source)

DANN

Uncertain

0.98

PhyloP100

-0.92

PromoterAI

-0.044

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000070

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over