dbSNP rs1292165928: SLC29A3:c.1+8C>T (chr10-71319318-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018344.6(SLC29A3):c.1+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000465 in 645,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SLC29A3
NM_018344.6 splice_region, intron

Scores

Splicing: ADA: 0.00006821

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.312

Publications

0 publications found

Variant links:

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: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
dysosteosclerosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC29A3 links:

ENSG00000298105 (HGNC:):

ENSG00000298105 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 10-71319318-C-T is Benign according to our data. Variant chr10-71319318-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1928581.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC29A3	NM_018344.6	MANE Select	c.1+8C>T	splice_region intron	N/A	NP_060814.4
SLC29A3	NM_001363518.2		c.-647C>T	5_prime_UTR	Exon 1 of 6	NP_001350447.1	A0A2R8YDR8
SLC29A3	NM_001174098.2		c.1+8C>T	splice_region intron	N/A	NP_001167569.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC29A3	ENST00000373189.6	TSL:1 MANE Select	c.1+8C>T	splice_region intron	N/A	ENSP00000362285.5	Q9BZD2-1
SLC29A3	ENST00000479577.2	TSL:2	c.-647C>T	5_prime_UTR	Exon 1 of 6	ENSP00000493995.1	A0A2R8YDR8
SLC29A3	ENST00000697843.1		n.34C>T	non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000116

AC:

AN:

86250

AF XY:

0.0000203

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00

GnomAD4 exome

AF:

0.00000405

AC:

AN:

493648

Hom.:

Cov.:

AF XY:

0.00000742

AC XY:

AN XY:

269504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

11162

American (AMR)

AF:

0.0000363

AC:

AN:

27578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18110

East Asian (EAS)

AF:

0.00

AC:

AN:

25472

South Asian (SAS)

AF:

0.00

AC:

AN:

56722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

291530

Other (OTH)

AF:

0.0000360

AC:

AN:

27780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

H syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.31

PromoterAI

0.10

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000068

dbscSNV1_RF

Benign

0.0060

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over