chr10-71328021-C-T

Variant names:

• chr10-71328021-C-T
• rs10999776
• NM_018344.6:c.300+4967C>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.300+4967C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,960 control chromosomes in the GnomAD database, including 13,683 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 0.40 (13683 hom., cov: 32)
• Consequence: SLC29A3 NM_018344.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.433
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	NM_018344.6	MANE Select	c.300+4967C>T		intron	N/A	NP_060814.4
	SLC29A3	NM_001363518.2		c.66+4967C>T		intron	N/A	NP_001350447.1
	SLC29A3	NM_001174098.2		c.300+4967C>T		intron	N/A	NP_001167569.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	ENST00000373189.6	TSL:1 MANE Select	c.300+4967C>T		intron	N/A	ENSP00000362285.5
	SLC29A3	ENST00000479577.2	TSL:2	c.66+4967C>T		intron	N/A	ENSP00000493995.1
	SLC29A3	ENST00000642198.1		n.66+4967C>T		intron	N/A	ENSP00000494827.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60295 AN: 151842 Hom.: 13667 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.397 AC: 60345 AN: 151960 Hom.: 13683 Cov.: 32 AF XY: 0.393 AC XY: 29177 AN XY: 74266

African (AFR) AF: 0.629 AC: 26047 AN: 41390

American (AMR) AF: 0.249 AC: 3816 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3470

East Asian (EAS) AF: 0.258 AC: 1325 AN: 5140

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4818

European-Finnish (FIN) AF: 0.368 AC: 3892 AN: 10574

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21713 AN: 67950

Other (OTH) AF: 0.357 AC: 755 AN: 2112

Alfa AF: 0.339 Hom.: 25179

Bravo AF: 0.396

Asia WGS AF: 0.296 AC: 1029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.57
PhyloP100		0.43

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: rs10999776; hg19: chr10-73087778;