dbSNP rs56822323: SLC19A1:p.Gly341Asp (chr21-45530899-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. Synonymous variant affecting the same amino acid position (i.e. G341G) has been classified as Likely benign.

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

Publications

3 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A1	NM_194255.4 link	c.1022G>A	p.Gly341Asp	missense_variant	Exon 4 of 6	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9 link	c.1022G>A	p.Gly341Asp	missense_variant	Exon 4 of 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

African (AFR)

AF:

0.00

AC:

AN:

26630

American (AMR)

AF:

0.00

AC:

AN:

25178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18942

East Asian (EAS)

AF:

0.00

AC:

AN:

33280

South Asian (SAS)

AF:

0.00

AC:

AN:

68216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47028

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5226

European-Non Finnish (NFE)

AF:

9.52e-7

AC:

AN:

1050084

Other (OTH)

AF:

0.00

AC:

AN:

54402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151598

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41258

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5026

South Asian (SAS)

AF:

0.00

AC:

AN:

4802

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67880

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

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

(source)

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;.

PhyloP100

-0.55

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

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over