10-71356184-TG-CA

Variant names:

• chr10-71356184-TG-CA
• rs34040486
• NM_018344.6:c.714_715delTGinsCA

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_018344.6(SLC29A3):​c.714_715delTGinsCA​(p.Val239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T238T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC29A3 NM_018344.6 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3 O:1
• Conservation: PhyloP100: 0.160
• Publications: 15 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: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• dysosteosclerosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 10-71356184-TG-CA is Benign according to our data. Variant chr10-71356184-TG-CA is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 300363.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	NM_018344.6	MANE Select	c.714_715delTGinsCA	p.Val239Ile	missense	N/A	NP_060814.4
	SLC29A3	NM_001363518.2		c.480_481delTGinsCA	p.Val161Ile	missense	N/A	NP_001350447.1
	SLC29A3	NM_001174098.2		c.714_715delTGinsCA	p.Val239Ile	missense	N/A	NP_001167569.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	ENST00000373189.6	TSL:1 MANE Select	c.714_715delTGinsCA	p.Val239Ile	missense	N/A	ENSP00000362285.5
	SLC29A3	ENST00000479577.2	TSL:2	c.480_481delTGinsCA	p.Val161Ile	missense	N/A	ENSP00000493995.1
	SLC29A3	ENST00000469204.1	TSL:2	n.205_206delTGinsCA		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34040486; hg19: chr10-73115941; COSMIC: COSV108214995;