NM_006996.3:c.204+2711C>T

Variant names:

• chr1-169482852-G-A
• rs17518769
• NM_006996.3:c.204+2711C>T

Variant summary

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

The NM_006996.3(SLC19A2):​c.204+2711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,030 control chromosomes in the GnomAD database, including 1,812 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 0.13 (1812 hom., cov: 32)
• Consequence: SLC19A2 NM_006996.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0270
• Publications: 4 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.252 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.204+2711C>T		intron	N/A	NP_008927.1	O60779-1
	SLC19A2	NM_001319667.1		c.204+2711C>T		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.204+2711C>T		intron	N/A	ENSP00000236137.5	O60779-1
	SLC19A2	ENST00000367804.4	TSL:1	c.204+2711C>T		intron	N/A	ENSP00000356778.3	O60779-2
	SLC19A2	ENST00000646596.1		c.204+2711C>T		intron	N/A	ENSP00000494404.1	A0A2R8Y5B5

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19877 AN: 151912 Hom.: 1807 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0571

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.131 AC: 19907 AN: 152030 Hom.: 1812 Cov.: 32 AF XY: 0.128 AC XY: 9491 AN XY: 74334

African (AFR) AF: 0.256 AC: 10620 AN: 41416

American (AMR) AF: 0.101 AC: 1543 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 571 AN: 3472

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5176

South Asian (SAS) AF: 0.104 AC: 504 AN: 4826

European-Finnish (FIN) AF: 0.0571 AC: 603 AN: 10568

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0820 AC: 5577 AN: 67972

Other (OTH) AF: 0.133 AC: 280 AN: 2112

Alfa AF: 0.100 Hom.: 1623

Bravo AF: 0.140

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.77
PhyloP100		0.027
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: rs17518769; hg19: chr1-169452090;