1-169468942-A-C

Variant names:

• chr1-169468942-A-C
• rs3737683
• NM_006996.3:c.1031-106T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006996.3(SLC19A2):​c.1031-106T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 830,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: SLC19A2 NM_006996.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• thiamine-responsive megaloblastic anemia syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Genomics England PanelApp

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A2	NM_006996.3	c.1031-106T>G		intron_variant	Intron 3 of 5	ENST00000236137.10	NP_008927.1
SLC19A2	NM_001319667.1	c.428-106T>G		intron_variant	Intron 2 of 4		NP_001306596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A2	ENST00000236137.10	c.1031-106T>G		intron_variant	Intron 3 of 5	1	NM_006996.3	ENSP00000236137.5
SLC19A2	ENST00000367804.4	c.428-106T>G		intron_variant	Intron 2 of 4	1		ENSP00000356778.3
SLC19A2	ENST00000643377.1	n.256T>G		non_coding_transcript_exon_variant	Exon 1 of 2
SLC19A2	ENST00000646596.1	c.1031-205T>G		intron_variant	Intron 3 of 5			ENSP00000494404.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 830554 Hom.: 0 Cov.: 11 AF XY: 0.00000231 AC XY: 1 AN XY: 432332

African (AFR) AF: 0.00 AC: 0 AN: 19804

American (AMR) AF: 0.00 AC: 0 AN: 32770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20976

East Asian (EAS) AF: 0.00 AC: 0 AN: 33438

South Asian (SAS) AF: 0.00 AC: 0 AN: 65522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41990

Middle Eastern (MID) AF: 0.000327 AC: 1 AN: 3054

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 573822

Other (OTH) AF: 0.00 AC: 0 AN: 39178

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.74
PhyloP100		0.50
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

Other links and lift over

dbSNP: rs3737683; hg19: chr1-169438180;