10-71336479-C-T

Variant names:

• chr10-71336479-C-T
• rs12256138
• NM_018344.6:c.301-7730C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018344.6(SLC29A3):​c.301-7730C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,614 control chromosomes in the GnomAD database, including 9,072 homozygotes. 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: 𝑓 0.32 (9072 hom., cov: 30)
• Consequence: SLC29A3 NM_018344.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 6 publications found

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: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• dysosteosclerosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A3	NM_018344.6	c.301-7730C>T		intron_variant	Intron 2 of 5	ENST00000373189.6	NP_060814.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC29A3	ENST00000373189.6	c.301-7730C>T		intron_variant	Intron 2 of 5	1	NM_018344.6	ENSP00000362285.5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48356 AN: 151496 Hom.: 9070 Cov.: 30

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.347

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.319 AC: 48369 AN: 151614 Hom.: 9072 Cov.: 30 AF XY: 0.316 AC XY: 23407 AN XY: 74054

African (AFR) AF: 0.143 AC: 5931 AN: 41342

American (AMR) AF: 0.272 AC: 4139 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1251 AN: 3462

East Asian (EAS) AF: 0.0677 AC: 347 AN: 5128

South Asian (SAS) AF: 0.273 AC: 1310 AN: 4792

European-Finnish (FIN) AF: 0.445 AC: 4657 AN: 10464

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.434 AC: 29477 AN: 67902

Other (OTH) AF: 0.347 AC: 729 AN: 2098

Alfa AF: 0.385 Hom.: 17417

Bravo AF: 0.295

Asia WGS AF: 0.212 AC: 737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.47
PhyloP100		-1.1

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

dbSNP: rs12256138; hg19: chr10-73096236;