NM_018344.6:c.1+80G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018344.6(SLC29A3):​c.1+80G>A variant causes a intron 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_018344.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.438
• 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• dysosteosclerosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000298105 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	NM_018344.6	MANE Select	c.1+80G>A		intron	N/A	NP_060814.4
	SLC29A3	NM_001363518.2		c.-575G>A		5_prime_UTR	Exon 1 of 6	NP_001350447.1	A0A2R8YDR8
	SLC29A3	NM_001174098.2		c.1+80G>A		intron	N/A	NP_001167569.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	ENST00000373189.6	TSL:1 MANE Select	c.1+80G>A		intron	N/A	ENSP00000362285.5	Q9BZD2-1
	SLC29A3	ENST00000479577.2	TSL:2	c.-575G>A		5_prime_UTR	Exon 1 of 6	ENSP00000493995.1	A0A2R8YDR8
	SLC29A3	ENST00000642198.1		n.-575G>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000494827.1	A0A2R8Y5U2

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

African (AFR) AF: 0.649 AC: 5978 AN: 9204

American (AMR) AF: 0.383 AC: 5953 AN: 15528

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 5793 AN: 13626

East Asian (EAS) AF: 0.426 AC: 10560 AN: 24778

South Asian (SAS) AF: 0.464 AC: 21001 AN: 45254

European-Finnish (FIN) AF: 0.454 AC: 13725 AN: 30206

Middle Eastern (MID) AF: 0.393 AC: 775 AN: 1972

European-Non Finnish (NFE) AF: 0.414 AC: 107640 AN: 259932

Other (OTH) AF: 0.437 AC: 10775 AN: 24644

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

African (AFR) AF: 0.645 AC: 26721 AN: 41420

American (AMR) AF: 0.390 AC: 5953 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1493 AN: 3468

East Asian (EAS) AF: 0.400 AC: 2045 AN: 5116

South Asian (SAS) AF: 0.456 AC: 2196 AN: 4818

European-Finnish (FIN) AF: 0.451 AC: 4756 AN: 10556

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27714 AN: 67880

Other (OTH) AF: 0.441 AC: 930 AN: 2108

Alfa AF: 0.434 Hom.: 1778

Bravo AF: 0.473

Asia WGS AF: 0.434 AC: 1508 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	8.6
DANN	Benign	0.89
PhyloP100		0.44
PromoterAI		-0.071	Neutral

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