Genetic Variant SLC29A3:c.-7C>T (chr10-71319303-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018344.6(SLC29A3):c.-7C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0009 in 644,634 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 15 hom. )

Consequence

SLC29A3
NM_018344.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63

Publications

0 publications found

Variant links:

Genes affected

SLC29A3 (HGNC:23096): (solute carrier family 29 member 3) This gene encodes a nucleoside transporter. The encoded protein plays a role in cellular uptake of nucleosides, nucleobases, and their related analogs. Mutations in this gene have been associated with H syndrome, which is characterized by cutaneous hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, and hypogonadism. A related disorder, PHID (pigmented hypertrichosis with insulin-dependent diabetes mellitus), has also been associated with mutations at this locus. Alternatively spliced transcript variants have been described.[provided by RefSeq, Mar 2010]

SLC29A3 Gene-Disease associations (from GenCC):

H syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
dysosteosclerosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC29A3 links:

ENSG00000298105 (HGNC:):

ENSG00000298105 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 10-71319303-C-T is Benign according to our data. Variant chr10-71319303-C-T is described in ClinVar as Benign. ClinVar VariationId is 877161.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000578 (88/152206) while in subpopulation SAS AF = 0.00621 (30/4834). AF 95% confidence interval is 0.00447. There are 0 homozygotes in GnomAd4. There are 56 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018344.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC29A3	NM_018344.6	MANE Select	c.-7C>T	5_prime_UTR	Exon 1 of 6	NP_060814.4
SLC29A3	NM_001363518.2		c.-662C>T	5_prime_UTR	Exon 1 of 6	NP_001350447.1	A0A2R8YDR8
SLC29A3	NM_001174098.2		c.-7C>T	5_prime_UTR	Exon 1 of 6	NP_001167569.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC29A3	ENST00000373189.6	TSL:1 MANE Select	c.-7C>T	5_prime_UTR	Exon 1 of 6	ENSP00000362285.5	Q9BZD2-1
SLC29A3	ENST00000479577.2	TSL:2	c.-662C>T	5_prime_UTR	Exon 1 of 6	ENSP00000493995.1	A0A2R8YDR8
SLC29A3	ENST00000642772.1		n.-7C>T	non_coding_transcript_exon	Exon 1 of 5	ENSP00000495041.1	A0A2R8Y4I0

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00599

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00183

AC:

157

AN:

85966

AF XY:

0.00244

show subpopulations

Gnomad AFR exome

AF:

0.00231

Gnomad AMR exome

AF:

0.000593

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000152

Gnomad OTH exome

AF:

0.00390

GnomAD4 exome

AF:

0.000999

AC:

492

AN:

492428

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

375

AN XY:

268958

show subpopulations

African (AFR)

AF:

0.00153

AC:

AN:

11078

American (AMR)

AF:

0.000551

AC:

AN:

27238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18102

East Asian (EAS)

AF:

0.0000396

AC:

AN:

25236

South Asian (SAS)

AF:

0.00714

AC:

404

AN:

56592

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33054

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

2308

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

291130

Other (OTH)

AF:

0.000686

AC:

AN:

27690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000578

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00113

AC:

AN:

41556

American (AMR)

AF:

0.000196

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67978

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

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:

0.000423

Hom.:

Bravo

AF:

0.000382

Asia WGS

AF:

0.00232

AC:

AN:

3468

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

H syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

-1.6

PromoterAI

-0.0017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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