rs3737683

Positions:

• chr1-169468942-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006996.3(SLC19A2):​c.1031-106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 982,534 control chromosomes in the GnomAD database, including 1,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (373 hom., cov: 32)
  • Exomes 𝑓: 0.051 (1382 hom.)
• Consequence: SLC19A2 NM_006996.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.499

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-169468942-A-G is Benign according to our data. Variant chr1-169468942-A-G is described in ClinVar as [Benign]. Clinvar id is 676194.Status of the report is criteria_provided_single_submitter, 1 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	c.1031-106T>C		intron_variant		ENST00000236137.10	NP_008927.1
SLC19A2	NM_001319667.1	c.428-106T>C		intron_variant			NP_001306596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A2	ENST00000236137.10	c.1031-106T>C		intron_variant		1	NM_006996.3	ENSP00000236137	P1
SLC19A2	ENST00000367804.4	c.428-106T>C		intron_variant		1		ENSP00000356778
SLC19A2	ENST00000646596.1	c.1031-205T>C		intron_variant				ENSP00000494404
SLC19A2	ENST00000643377.1	n.256T>C		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.0614 AC: 9347 AN: 152136 Hom.: 372 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0529

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0791

Gnomad FIN AF: 0.00489

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0579

GnomAD4 exome AF: 0.0509 AC: 42301 AN: 830280 Hom.: 1382 Cov.: 11 AF XY: 0.0520 AC XY: 22468 AN XY: 432192

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0392

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.0944

Gnomad4 SAS exome AF: 0.0726

Gnomad4 FIN exome AF: 0.00681

Gnomad4 NFE exome AF: 0.0443

Gnomad4 OTH exome AF: 0.0658

GnomAD4 genome AF: 0.0614 AC: 9356 AN: 152254 Hom.: 373 Cov.: 32 AF XY: 0.0610 AC XY: 4541 AN XY: 74464

Gnomad4 AFR AF: 0.0957

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0795

Gnomad4 FIN AF: 0.00489

Gnomad4 NFE AF: 0.0432

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0490 Hom.: 19

Bravo AF: 0.0665

Asia WGS AF: 0.0970 AC: 338 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.7
DANN	Benign	0.77
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

Other links and lift over

dbSNP: rs3737683; hg19: chr1-169438180;