NM_018344.6:c.1+162T>C

Variant names:

• chr10-71319472-T-C
• rs41300554
• NM_018344.6:c.1+162T>C

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+162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 441,496 control chromosomes in the GnomAD database, including 46,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18186 hom., cov: 32)
  • Exomes 𝑓: 0.44 (28074 hom.)
• Consequence: SLC29A3 NM_018344.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.101
• Publications: 4 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

ENSG00000298105 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 10-71319472-T-C is Benign according to our data. Variant chr10-71319472-T-C is described in ClinVar as Benign. ClinVar VariationId is 1272485.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+162T>C		intron	N/A	NP_060814.4
	SLC29A3	NM_001363518.2		c.-493T>C		5_prime_UTR	Exon 1 of 6	NP_001350447.1	A0A2R8YDR8
	SLC29A3	NM_001174098.2		c.1+162T>C		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+162T>C		intron	N/A	ENSP00000362285.5	Q9BZD2-1
	SLC29A3	ENST00000479577.2	TSL:2	c.-493T>C		5_prime_UTR	Exon 1 of 6	ENSP00000493995.1	A0A2R8YDR8
	SLC29A3	ENST00000642198.1		n.-493T>C		non_coding_transcript_exon	Exon 1 of 6	ENSP00000494827.1	A0A2R8Y5U2

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72482 AN: 151736 Hom.: 18176 Cov.: 32

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.437 AC: 126431 AN: 289642 Hom.: 28074 Cov.: 0 AF XY: 0.436 AC XY: 66680 AN XY: 152958

African (AFR) AF: 0.641 AC: 4363 AN: 6806

American (AMR) AF: 0.347 AC: 2525 AN: 7274

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 3990 AN: 9288

East Asian (EAS) AF: 0.425 AC: 9378 AN: 22082

South Asian (SAS) AF: 0.503 AC: 9725 AN: 19320

European-Finnish (FIN) AF: 0.477 AC: 11454 AN: 24024

Middle Eastern (MID) AF: 0.396 AC: 542 AN: 1368

European-Non Finnish (NFE) AF: 0.421 AC: 76547 AN: 181690

Other (OTH) AF: 0.444 AC: 7907 AN: 17790

GnomAD4 genome AF: 0.478 AC: 72532 AN: 151854 Hom.: 18186 Cov.: 32 AF XY: 0.477 AC XY: 35435 AN XY: 74216

African (AFR) AF: 0.646 AC: 26733 AN: 41406

American (AMR) AF: 0.390 AC: 5956 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2056 AN: 5136

South Asian (SAS) AF: 0.456 AC: 2198 AN: 4822

European-Finnish (FIN) AF: 0.464 AC: 4880 AN: 10518

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

European-Non Finnish (NFE) AF: 0.409 AC: 27762 AN: 67918

Other (OTH) AF: 0.441 AC: 929 AN: 2108

Alfa AF: 0.431 Hom.: 2911

Bravo AF: 0.473

Asia WGS AF: 0.437 AC: 1520 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.5
DANN	Benign	0.75
PhyloP100		-0.10
PromoterAI		0.036	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: rs41300554; hg19: chr10-73079229; COSMIC: COSV64384769; COSMIC: COSV64384769;