Variant chr21-45515870-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_194255.4(SLC19A1):c.1564G>A(p.Asp522Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,580,390 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00086 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

SLC19A1
NM_194255.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005077362).

BP6

Variant 21-45515870-C-T is Benign according to our data. Variant chr21-45515870-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 719308.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_194255.4 linkuse as main transcript	c.1564G>A	p.Asp522Asn	missense_variant	6/6	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.1564G>A	p.Asp522Asn	missense_variant	6/6	1	NM_194255.4	ENSP00000308895.4		P41440-1

Frequencies

GnomAD3 genomes

AF:

0.000867

AC:

132

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000443

AC:

AN:

205522

Hom.:

AF XY:

0.000422

AC XY:

AN XY:

111426

show subpopulations

Gnomad AFR exome

AF:

0.00321

Gnomad AMR exome

AF:

0.000240

Gnomad ASJ exome

AF:

0.00222

Gnomad EAS exome

AF:

0.000121

Gnomad SAS exome

AF:

0.0000403

Gnomad FIN exome

AF:

0.0000560

Gnomad NFE exome

AF:

0.000219

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000203

AC:

290

AN:

1428070

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

147

AN XY:

706998

show subpopulations

Gnomad4 AFR exome

AF:

0.00247

Gnomad4 AMR exome

AF:

0.000248

Gnomad4 ASJ exome

AF:

0.00200

Gnomad4 EAS exome

AF:

0.000154

Gnomad4 SAS exome

AF:

0.0000611

Gnomad4 FIN exome

AF:

0.0000782

Gnomad4 NFE exome

AF:

0.000111

Gnomad4 OTH exome

AF:

0.000238

GnomAD4 genome

AF:

0.000860

AC:

131

AN:

152320

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000350

Hom.:

Bravo

AF:

0.000948

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00251

AC:

ESP6500EA

AF:

0.000466

AC:

ExAC

AF:

0.000456

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.0051

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.41

N;N

REVEL

Benign

0.075

Sift

Benign

0.054

T;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.92

P;.

Vest4

0.18

MVP

0.27

MPC

0.27

ClinPred

0.024

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.072

gMVP

0.084

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over