10-71322900-G-C

Variant names:

• chr10-71322900-G-C
• rs201610819
• NM_018344.6:c.146G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018344.6(SLC29A3):​c.146G>C​(p.Arg49Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R49H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: SLC29A3 NM_018344.6 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:4
• Conservation: PhyloP100: 0.819
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1598461).

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.146G>C	p.Arg49Pro	missense	Exon 2 of 6	NP_060814.4
	SLC29A3	NM_001174098.2		c.146G>C	p.Arg49Pro	missense	Exon 2 of 6	NP_001167569.1
	SLC29A3	NM_001363518.2		c.-89G>C		5_prime_UTR	Exon 2 of 6	NP_001350447.1	A0A2R8YDR8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC29A3	ENST00000373189.6	TSL:1 MANE Select	c.146G>C	p.Arg49Pro	missense	Exon 2 of 6	ENSP00000362285.5	Q9BZD2-1
	SLC29A3	ENST00000479577.2	TSL:2	c.-89G>C		5_prime_UTR	Exon 2 of 6	ENSP00000493995.1	A0A2R8YDR8
	SLC29A3	ENST00000642198.1		n.-89G>C		non_coding_transcript_exon	Exon 2 of 6	ENSP00000494827.1	A0A2R8Y5U2

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152256 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000199 AC: 50 AN: 251348 AF XY: 0.000132

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000383 AC: 56 AN: 1461868 Hom.: 0 Cov.: 35 AF XY: 0.0000275 AC XY: 20 AN XY: 727234

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00125 AC: 56 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000984 AC: 15 AN: 152374 Hom.: 0 Cov.: 34 AF XY: 0.000121 AC XY: 9 AN XY: 74508

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.000849 AC: 13 AN: 15308

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000234

ExAC AF: 0.000107 AC: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.16	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.82
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.69
MVP		0.90
MPC		0.41
ClinPred		0.40	T
GERP RS		3.4
Varity_R		0.65
gMVP		0.83

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: rs201610819; hg19: chr10-73082657;