Menu
GeneBe

rs1051266

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_194255.4(SLC19A1):c.80A>C(p.His27Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H27R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC19A1
NM_194255.4 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.987
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.17784226).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC19A1NM_194255.4 linkuse as main transcriptc.80A>C p.His27Pro missense_variant 2/6 ENST00000311124.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC19A1ENST00000311124.9 linkuse as main transcriptc.80A>C p.His27Pro missense_variant 2/61 NM_194255.4 A2P41440-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000437
AC:
1
AN:
228958
Hom.:
0
AF XY:
0.00000803
AC XY:
1
AN XY:
124500
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000580
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.90e-7
AC:
1
AN:
1448858
Hom.:
0
Cov.:
46
AF XY:
0.00000139
AC XY:
1
AN XY:
719954
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
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
0.080
BayesDel_addAF
Benign
-0.079
T
BayesDel_noAF
Benign
-0.17
Cadd
Benign
11
Dann
Benign
0.40
DEOGEN2
Benign
0.17
T;T;.;T;.;T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.29
T;T;T;T;T;T
M_CAP
Uncertain
0.093
D
MetaRNN
Benign
0.18
T;T;T;T;T;T
MetaSVM
Benign
-0.69
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.4
N;N;N;N;N;N
Sift
Benign
0.20
T;T;T;T;T;T
Sift4G
Benign
0.20
T;T;T;.;.;.
Polyphen
0.0040
.;B;.;.;.;.
Vest4
0.10
MutPred
0.46
Gain of catalytic residue at H27 (P = 0.0695);Gain of catalytic residue at H27 (P = 0.0695);Gain of catalytic residue at H27 (P = 0.0695);Gain of catalytic residue at H27 (P = 0.0695);Gain of catalytic residue at H27 (P = 0.0695);Gain of catalytic residue at H27 (P = 0.0695);
MVP
0.84
MPC
0.15
ClinPred
0.0072
T
GERP RS
2.8
Varity_R
0.10
gMVP
0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1051266; hg19: chr21-46957794; API