Genetic Variant SLC29A3:c.-7C>A (chr10-71319303-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018344.6(SLC29A3):c.-7C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000203 in 492,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000020 ( 0 hom. )

Consequence

SLC29A3
NM_018344.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

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>A	5_prime_UTR	Exon 1 of 6	NP_060814.4
SLC29A3	NM_001363518.2		c.-662C>A	5_prime_UTR	Exon 1 of 6	NP_001350447.1	A0A2R8YDR8
SLC29A3	NM_001174098.2		c.-7C>A	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>A	5_prime_UTR	Exon 1 of 6	ENSP00000362285.5	Q9BZD2-1
SLC29A3	ENST00000479577.2	TSL:2	c.-662C>A	5_prime_UTR	Exon 1 of 6	ENSP00000493995.1	A0A2R8YDR8
SLC29A3	ENST00000642772.1		n.-7C>A	non_coding_transcript_exon	Exon 1 of 5	ENSP00000495041.1	A0A2R8Y4I0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000203

AC:

AN:

492434

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

268964

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11078

American (AMR)

AF:

0.00

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:

0.00

AC:

AN:

56594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

291134

Other (OTH)

AF:

0.00

AC:

AN:

27690

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

-1.6

PromoterAI

-0.18

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over