chr10-71319545-C-G

Variant names:

• chr10-71319545-C-G
• rs7067937
• NM_018344.6:c.1+235C>G

Variant summary

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

The NM_001363518.2(SLC29A3):​c.-420C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 407,542 control chromosomes in the GnomAD database, including 42,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18124 hom., cov: 32)
  • Exomes 𝑓: 0.43 (24175 hom.)
• Consequence: SLC29A3 NM_001363518.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.09
• Publications: 1 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=-0.81).
• BP6: Variant 10-71319545-C-G is Benign according to our data. Variant chr10-71319545-C-G is described in ClinVar as Benign. ClinVar VariationId is 1239908.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_001363518.2. 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+235C>G		intron	N/A	NP_060814.4
	SLC29A3	NM_001363518.2		c.-420C>G		5_prime_UTR	Exon 1 of 6	NP_001350447.1	A0A2R8YDR8
	SLC29A3	NM_001174098.2		c.1+235C>G		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+235C>G		intron	N/A	ENSP00000362285.5	Q9BZD2-1
	SLC29A3	ENST00000479577.2	TSL:2	c.-420C>G		5_prime_UTR	Exon 1 of 6	ENSP00000493995.1	A0A2R8YDR8
	SLC29A3	ENST00000642198.1		n.-420C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000494827.1	A0A2R8Y5U2

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72325 AN: 151844 Hom.: 18114 Cov.: 32

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.442

GnomAD4 exome AF: 0.429 AC: 109742 AN: 255580 Hom.: 24175 Cov.: 0 AF XY: 0.427 AC XY: 56611 AN XY: 132530

African (AFR) AF: 0.640 AC: 4179 AN: 6532

American (AMR) AF: 0.342 AC: 2336 AN: 6832

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 3737 AN: 8744

East Asian (EAS) AF: 0.425 AC: 9156 AN: 21520

South Asian (SAS) AF: 0.502 AC: 5182 AN: 10326

European-Finnish (FIN) AF: 0.459 AC: 9902 AN: 21570

Middle Eastern (MID) AF: 0.392 AC: 492 AN: 1254

European-Non Finnish (NFE) AF: 0.416 AC: 67663 AN: 162578

Other (OTH) AF: 0.437 AC: 7095 AN: 16224

GnomAD4 genome AF: 0.476 AC: 72375 AN: 151962 Hom.: 18124 Cov.: 32 AF XY: 0.475 AC XY: 35300 AN XY: 74250

African (AFR) AF: 0.645 AC: 26709 AN: 41402

American (AMR) AF: 0.390 AC: 5970 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1496 AN: 3472

East Asian (EAS) AF: 0.401 AC: 2073 AN: 5166

South Asian (SAS) AF: 0.456 AC: 2192 AN: 4810

European-Finnish (FIN) AF: 0.450 AC: 4739 AN: 10532

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

European-Non Finnish (NFE) AF: 0.408 AC: 27742 AN: 67960

Other (OTH) AF: 0.440 AC: 931 AN: 2114

Alfa AF: 0.449 Hom.: 1943

Bravo AF: 0.473

Asia WGS AF: 0.435 AC: 1512 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	-0.81
CADD	Benign	8.8
DANN	Benign	0.69
PhyloP100		1.1
PromoterAI		0.051	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7067937; hg19: chr10-73079302; COSMIC: COSV64384773; COSMIC: COSV64384773;