rs16928722

Variant names:

• chr10-71337752-G-T
• rs16928722
• NM_018344.6:c.301-6457G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_018344.6(SLC29A3):​c.301-6457G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0564 in 152,276 control chromosomes in the GnomAD database, including 367 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 0.056 (367 hom., cov: 33)
• Consequence: SLC29A3 NM_018344.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A3	NM_018344.6	c.301-6457G>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.301-6457G>T		intron_variant	Intron 2 of 5	1	NM_018344.6	ENSP00000362285.5

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8599 AN: 152158 Hom.: 367 Cov.: 33

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.0353

Gnomad ASJ AF: 0.0455

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.0899

Gnomad FIN AF: 0.0907

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.0526

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

GnomAD4 genome AF: 0.0564 AC: 8585 AN: 152276 Hom.: 367 Cov.: 33 AF XY: 0.0598 AC XY: 4455 AN XY: 74456

African (AFR) AF: 0.0327 AC: 1358 AN: 41560

American (AMR) AF: 0.0352 AC: 539 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0455 AC: 158 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1113 AN: 5164

South Asian (SAS) AF: 0.0888 AC: 428 AN: 4822

European-Finnish (FIN) AF: 0.0907 AC: 962 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0553 AC: 3765 AN: 68026

Other (OTH) AF: 0.0526 AC: 111 AN: 2112

Alfa AF: 0.0557 Hom.: 124

Bravo AF: 0.0511

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	19
DANN	Benign	0.73
PhyloP100		2.1

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: rs16928722; hg19: chr10-73097509;