Variant chr1-169464035-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBA1

The NM_006996.3(SLC19A2):c.*1814G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 152,418 control chromosomes in the GnomAD database, including 367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.061 ( 367 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

SLC19A2
NM_006996.3 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.42

Variant links:

Genes affected

SLC19A2 (HGNC:10938): (solute carrier family 19 member 2) This gene encodes the thiamin transporter protein. Mutations in this gene cause thiamin-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

SLC19A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.12).

BP6

Variant 1-169464035-C-T is Benign according to our data. Variant chr1-169464035-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 293507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A2	NM_006996.3 linkuse as main transcript	c.*1814G>A		3_prime_UTR_variant	6/6	ENST00000236137.10	NP_008927.1
SLC19A2	NM_001319667.1 linkuse as main transcript	c.*1814G>A		3_prime_UTR_variant	5/5		NP_001306596.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A2	ENST00000236137.10 linkuse as main transcript	c.*1814G>A	3_prime_UTR_variant	6/6	1	NM_006996.3	ENSP00000236137	P1	O60779-1
SLC19A2	ENST00000367804.4 linkuse as main transcript	c.*1814G>A	3_prime_UTR_variant	5/5	1		ENSP00000356778		O60779-2
SLC19A2	ENST00000643377.1 linkuse as main transcript	n.3030G>A	non_coding_transcript_exon_variant	2/2
SLC19A2	ENST00000646596.1 linkuse as main transcript		downstream_gene_variant				ENSP00000494404

Frequencies

GnomAD3 genomes

AF:

0.0611

AC:

9282

AN:

151868

Hom.:

366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0944

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0530

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.0787

Gnomad FIN

AF:

0.00485

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0432

Gnomad OTH

AF:

0.0589

GnomAD4 exome

AF:

0.00231

AC:

AN:

432

Hom.:

Cov.:

AF XY:

0.00385

AC XY:

AN XY:

260

show subpopulations

Gnomad4 FIN exome

AF:

0.00235

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0611

AC:

9291

AN:

151986

Hom.:

367

Cov.:

AF XY:

0.0607

AC XY:

4507

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0944

Gnomad4 AMR

AF:

0.0528

Gnomad4 ASJ

AF:

0.115

Gnomad4 EAS

AF:

0.120

Gnomad4 SAS

AF:

0.0789

Gnomad4 FIN

AF:

0.00485

Gnomad4 NFE

AF:

0.0432

Gnomad4 OTH

AF:

0.0601

Alfa

AF:

0.0503

Hom.:

Bravo

AF:

0.0660

Asia WGS

AF:

0.0960

AC:

334

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Megaloblastic anemia, thiamine-responsive, with diabetes mellitus and sensorineural deafness

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Thiamine-responsive megaloblastic anemia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.71

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over