10-71319390-G-A

Variant names:

• chr10-71319390-G-A
• rs17525188
• NM_018344.6:c.1+80G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001363518.2(SLC29A3):​c.-575G>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 0.441 in 576,992 control chromosomes in the GnomAD database, including 57,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18111 hom., cov: 32)
  • Exomes 𝑓: 0.43 (39820 hom.)
• Consequence: SLC29A3 NM_001363518.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.438

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]

LOC124902445 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-71319390-G-A is Benign according to our data. Variant chr10-71319390-G-A is described in ClinVar as [Benign]. Clinvar id is 1220931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC29A3	NM_018344.6	c.1+80G>A		intron_variant	Intron 1 of 5	ENST00000373189.6	NP_060814.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC29A3	ENST00000373189.6	c.1+80G>A		intron_variant	Intron 1 of 5	1	NM_018344.6	ENSP00000362285.5

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72282 AN: 151732 Hom.: 18101 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.429 AC: 182200 AN: 425144 Hom.: 39820 Cov.: 0 AF XY: 0.427 AC XY: 99029 AN XY: 231730

Gnomad4 AFR exome AF: 0.649

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.426

Gnomad4 SAS exome AF: 0.464

Gnomad4 FIN exome AF: 0.454

Gnomad4 NFE exome AF: 0.414

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.476 AC: 72332 AN: 151848 Hom.: 18111 Cov.: 32 AF XY: 0.476 AC XY: 35307 AN XY: 74230

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.441

Alfa AF: 0.434 Hom.: 1778

Bravo AF: 0.473

Asia WGS AF: 0.434 AC: 1508 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 48% of patients studied by a panel of primary immunodeficiencies. Number of patients: 42. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.6
DANN	Benign	0.89

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

LitVar

Other links and lift over

dbSNP: rs17525188; hg19: chr10-73079147; COSMIC: COSV64384644; COSMIC: COSV64384644;