rs77626641

Variant names:

• chr10-71344297-C-T
• rs77626641
• NM_018344.6:c.383+6C>T

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.383+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00269 in 1,609,496 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (161 hom.)
• Consequence: SLC29A3 NM_018344.6 splice_region, intron
• Scores: Splicing: ADA: 0.00005683
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.876
• Publications: 2 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: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia
• dysosteosclerosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289607 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-71344297-C-T is Benign according to our data. Variant chr10-71344297-C-T is described in ClinVar as Benign. ClinVar VariationId is 300358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0765 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.383+6C>T		splice_region intron	N/A	NP_060814.4
	SLC29A3	NM_001363518.2		c.149+6C>T		splice_region intron	N/A	NP_001350447.1	A0A2R8YDR8
	SLC29A3	NM_001174098.2		c.383+6C>T		splice_region 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.383+6C>T		splice_region intron	N/A	ENSP00000362285.5	Q9BZD2-1
	SLC29A3	ENST00000479577.2	TSL:2	c.149+6C>T		splice_region intron	N/A	ENSP00000493995.1	A0A2R8YDR8
	SLC29A3	ENST00000642198.1		n.67-7265C>T		intron	N/A	ENSP00000494827.1	A0A2R8Y5U2

Frequencies

GnomAD3 genomes AF: 0.00269 AC: 409 AN: 152186 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0539

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00573 AC: 1440 AN: 251164 AF XY: 0.00493

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.0116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0520

Gnomad FIN exome AF: 0.0000935

Gnomad NFE exome AF: 0.000281

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00269 AC: 3918 AN: 1457192 Hom.: 161 Cov.: 30 AF XY: 0.00254 AC XY: 1844 AN XY: 725338

African (AFR) AF: 0.000389 AC: 13 AN: 33392

American (AMR) AF: 0.0108 AC: 481 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26118

East Asian (EAS) AF: 0.0788 AC: 3125 AN: 39668

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86174

European-Finnish (FIN) AF: 0.000132 AC: 7 AN: 53176

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5756

European-Non Finnish (NFE) AF: 0.000122 AC: 135 AN: 1107928

Other (OTH) AF: 0.00197 AC: 119 AN: 60266

GnomAD4 genome AF: 0.00269 AC: 409 AN: 152304 Hom.: 12 Cov.: 32 AF XY: 0.00321 AC XY: 239 AN XY: 74468

African (AFR) AF: 0.000481 AC: 20 AN: 41558

American (AMR) AF: 0.00640 AC: 98 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0534 AC: 276 AN: 5166

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68038

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000581 Hom.: 0

Bravo AF: 0.00331

Asia WGS AF: 0.0280 AC: 97 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	H syndrome (2)
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	SLC29A3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	15
DANN	Benign	0.47
PhyloP100		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.016
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: rs77626641; hg19: chr10-73104054; COSMIC: COSV64385173;