chr1-169468154-A-T

Variant names:

• chr1-169468154-A-T
• NM_006996.3:c.1322T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006996.3(SLC19A2):​c.1322T>A​(p.Ile441Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I441T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC19A2 NM_006996.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.15

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A2	NM_006996.3	c.1322T>A	p.Ile441Asn	missense_variant	Exon 5 of 6	ENST00000236137.10	NP_008927.1
SLC19A2	NM_001319667.1	c.719T>A	p.Ile240Asn	missense_variant	Exon 4 of 5		NP_001306596.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A2	ENST00000236137.10	c.1322T>A	p.Ile441Asn	missense_variant	Exon 5 of 6	1	NM_006996.3	ENSP00000236137.5
SLC19A2	ENST00000367804.4	c.719T>A	p.Ile240Asn	missense_variant	Exon 4 of 5	1		ENSP00000356778.3
SLC19A2	ENST00000646596.1	c.1223T>A	p.Ile408Asn	missense_variant	Exon 5 of 6			ENSP00000494404.1
SLC19A2	ENST00000643377.1	n.1044T>A		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.85	D;.;D;.
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D;D;.;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.82	D;D;D;D
MetaSVM	Pathogenic	0.84	D
MutationAssessor	Pathogenic	3.4	M;.;M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-5.9	D;D;.;.
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D;D;.;.
Sift4G	Pathogenic	0.0010	D;D;.;.
Polyphen		1.0	D;D;D;.
Vest4		0.96
MutPred		0.65		Loss of stability (P = 0.0053);.;Loss of stability (P = 0.0053);.;
MVP		0.94
MPC		0.84
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.90
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-169437392;