NM_006996.3:c.1365+803A>G

Variant names:

• chr1-169467308-T-C
• rs6656822
• NM_006996.3:c.1365+803A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006996.3(SLC19A2):​c.1365+803A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,108 control chromosomes in the GnomAD database, including 40,149 homozygotes. 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: 𝑓 0.72 (40149 hom., cov: 32)
• Consequence: SLC19A2 NM_006996.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.452
• Publications: 12 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, Genomics England PanelApp, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006996.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC19A2	NM_006996.3	MANE Select	c.1365+803A>G		intron	N/A	NP_008927.1	O60779-1
	SLC19A2	NM_001319667.1		c.762+803A>G		intron	N/A	NP_001306596.1	A0A024R8Y5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC19A2	ENST00000236137.10	TSL:1 MANE Select	c.1365+803A>G		intron	N/A	ENSP00000236137.5	O60779-1
	SLC19A2	ENST00000367804.4	TSL:1	c.762+803A>G		intron	N/A	ENSP00000356778.3	O60779-2
	SLC19A2	ENST00000646596.1		c.1266+803A>G		intron	N/A	ENSP00000494404.1	A0A2R8Y5B5

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110149 AN: 151990 Hom.: 40087 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.762

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.729

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.725 AC: 110274 AN: 152108 Hom.: 40149 Cov.: 32 AF XY: 0.728 AC XY: 54140 AN XY: 74336

African (AFR) AF: 0.684 AC: 28387 AN: 41484

American (AMR) AF: 0.776 AC: 11843 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2821 AN: 3472

East Asian (EAS) AF: 0.936 AC: 4844 AN: 5174

South Asian (SAS) AF: 0.637 AC: 3074 AN: 4824

European-Finnish (FIN) AF: 0.762 AC: 8065 AN: 10578

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48776 AN: 67988

Other (OTH) AF: 0.732 AC: 1546 AN: 2112

Alfa AF: 0.720 Hom.: 65951

Bravo AF: 0.730

Asia WGS AF: 0.799 AC: 2781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.051
DANN	Benign	0.45
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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: rs6656822; hg19: chr1-169436546;