chr10-71323057-A-G

Position:

• chr10-71323057-A-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_018344.6(SLC29A3):​c.300+3A>G variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00191 in 1,612,724 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (30 hom., cov: 34)
  • Exomes 𝑓: 0.00099 (31 hom.)
• Consequence: SLC29A3 NM_018344.6 splice_donor_region, intron
• Scores: Splicing: ADA: 0.8215
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.20

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 10-71323057-A-G is Benign according to our data. Variant chr10-71323057-A-G is described in ClinVar as [Benign]. Clinvar id is 300357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-71323057-A-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1637/152362) while in subpopulation AFR AF= 0.0378 (1571/41588). AF 95% confidence interval is 0.0362. There are 30 homozygotes in gnomad4. There are 754 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC29A3	NM_018344.6	c.300+3A>G		splice_donor_region_variant, intron_variant		ENST00000373189.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC29A3	ENST00000373189.6	c.300+3A>G		splice_donor_region_variant, intron_variant		1	NM_018344.6	P1

Frequencies

GnomAD3 genomes AF: 0.0107 AC: 1635 AN: 152244 Hom.: 30 Cov.: 34

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00261 AC: 649 AN: 248240 Hom.: 13 AF XY: 0.00181 AC XY: 244 AN XY: 134512

Gnomad AFR exome AF: 0.0362

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000180

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000988 AC: 1443 AN: 1460362 Hom.: 31 Cov.: 35 AF XY: 0.000796 AC XY: 578 AN XY: 726486

Gnomad4 AFR exome AF: 0.0358

Gnomad4 AMR exome AF: 0.00114

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000621

Gnomad4 OTH exome AF: 0.00191

GnomAD4 genome AF: 0.0107 AC: 1637 AN: 152362 Hom.: 30 Cov.: 34 AF XY: 0.0101 AC XY: 754 AN XY: 74514

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.00202

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00561 Hom.: 8

Bravo AF: 0.0119

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

H syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 28, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.82
dbscSNV1_RF	Benign	0.48
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7083031; hg19: chr10-73082814;