rs1051266

Variant names:

• chr21-45537880-T-A
• NM_194255.4:c.80A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-45537880-T-A
• chr21-45537880-T-C
• chr21-45537880-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194255.4(SLC19A1):​c.80A>T​(p.His27Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC19A1 NM_194255.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987

Genes affected

SLC19A1 (HGNC:10937): (solute carrier family 19 member 1) The membrane protein encoded by this gene is a transporter of folate and is involved in the regulation of intracellular concentrations of folate. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0782066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.80A>T	p.His27Leu	missense_variant	Exon 2 of 6	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9	c.80A>T	p.His27Leu	missense_variant	Exon 2 of 6	1	NM_194255.4	ENSP00000308895.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1448858 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 719954

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	3.7
DANN	Benign	0.39
DEOGEN2	Benign	0.13	T;T;.;T;.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.17	T;T;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.078	T;T;T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	-1.3	.;N;N;.;.;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.86	N;N;N;N;N;N
REVEL	Uncertain	0.33
Sift	Benign	0.64	T;T;T;T;T;T
Sift4G	Benign	0.65	T;T;T;.;.;.
Polyphen		0.0	.;B;.;.;.;.
Vest4		0.058
MutPred		0.35		Loss of disorder (P = 0.0768);Loss of disorder (P = 0.0768);Loss of disorder (P = 0.0768);Loss of disorder (P = 0.0768);Loss of disorder (P = 0.0768);Loss of disorder (P = 0.0768);
MVP		0.67
MPC		0.12
ClinPred		0.029	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.032
gMVP		0.37

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: chr21-46957794;