rs77339410

chr10-71344212-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018344.6(SLC29A3):c.304T>C(p.Tyr102His) variant causes a missense change. The variant allele was found at a frequency of 0.00296 in 1,614,002 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (77 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (82 hom.)
• Consequence: SLC29A3 NM_018344.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 7.10

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005489558).
• BP6: Variant 10-71344212-T-C is Benign according to our data. Variant chr10-71344212-T-C is described in ClinVar as [Benign]. Clinvar id is 130335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC29A3	NM_018344.6	c.304T>C	p.Tyr102His	missense_variant	3/6	ENST00000373189.6
LOC105378353	XR_946051.3	n.167-2831A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC29A3	ENST00000373189.6	c.304T>C	p.Tyr102His	missense_variant	3/6	1	NM_018344.6	P1
	ENST00000686111.2	n.228-2831A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2447 AN: 152186 Hom.: 76 Cov.: 32

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

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: 0.000176

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00428 AC: 1075 AN: 251440 Hom.: 30 AF XY: 0.00286 AC XY: 389 AN XY: 135894

Gnomad AFR exome AF: 0.0568

Gnomad AMR exome AF: 0.00341

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000132

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00160 AC: 2333 AN: 1461698 Hom.: 82 Cov.: 32 AF XY: 0.00140 AC XY: 1016 AN XY: 727170

Gnomad4 AFR exome AF: 0.0560

Gnomad4 AMR exome AF: 0.00362

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000405

Gnomad4 OTH exome AF: 0.00373

GnomAD4 genome AF: 0.0161 AC: 2451 AN: 152304 Hom.: 77 Cov.: 32 AF XY: 0.0152 AC XY: 1133 AN XY: 74482

Gnomad4 AFR AF: 0.0562

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00330 Hom.: 27

Bravo AF: 0.0176

ESP6500AA AF: 0.0604 AC: 266

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00539 AC: 655

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

H syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

-

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.24
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.016	T;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
MetaRNN	Benign	0.0055	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.9	M;M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.67	T
Polyphen		0.98	D;D;.
Vest4		0.73
MVP		0.72
MPC		0.40
ClinPred		0.026	T
GERP RS		5.9
Varity_R		0.13
gMVP		0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs77339410; hg19: chr10-73103969;