Variant chr21-45530899-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_194255.4(SLC19A1):c.1022G>A(p.Gly341Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000135 in 1,480,584 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

SLC19A1
NM_194255.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.554

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]

SLC19A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_194255.4 linkuse as main transcript	c.1022G>A	p.Gly341Asp	missense_variant	4/6	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9 linkuse as main transcript	c.1022G>A	p.Gly341Asp	missense_variant	4/6	1	NM_194255.4	ENSP00000308895.4		P41440-1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.52e-7

AC:

AN:

1328986

Hom.:

Cov.:

AF XY:

0.00000154

AC XY:

AN XY:

650284

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.52e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151598

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74000

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Benign

-0.16

CADD

Benign

0.76

DANN

Benign

0.74

DEOGEN2

Benign

0.26

T;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.82

T;T;T;T

M_CAP

Pathogenic

0.40

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.1

.;M;M;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Uncertain

0.58

Sift

Benign

0.16

T;T;T;T

Sift4G

Benign

0.063

T;T;T;D

Polyphen

0.26

.;B;.;.

Vest4

0.65

MutPred

0.62

Loss of MoRF binding (P = 0.0593);Loss of MoRF binding (P = 0.0593);Loss of MoRF binding (P = 0.0593);.;

MVP

0.41

MPC

1.0

ClinPred

0.16

GERP RS

-8.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.080

gMVP

0.81

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over