Genetic Variant SLC19A1:p.Pro232Pro (chr21-45531642-A-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_194255.4(SLC19A1):c.696T>G(p.Pro232Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P232P) has been classified as Benign.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC19A1
NM_194255.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.56

Publications

52 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 Gene-Disease associations (from GenCC):

combined immunodeficiency
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
immunodeficiency 114, folate-responsive
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
megaloblastic anemia, folate-responsive
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

SLC19A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP7

Synonymous conserved (PhyloP=-6.56 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194255.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC19A1	NM_194255.4	MANE Select	c.696T>G	p.Pro232Pro	synonymous	Exon 3 of 6	NP_919231.1	P41440-1
SLC19A1	NM_001352512.2		c.696T>G	p.Pro232Pro	synonymous	Exon 3 of 6	NP_001339441.1	P41440-1
SLC19A1	NM_001205207.3		c.576T>G	p.Pro192Pro	synonymous	Exon 2 of 5	NP_001192136.1	P41440-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC19A1	ENST00000311124.9	TSL:1 MANE Select	c.696T>G	p.Pro232Pro	synonymous	Exon 3 of 6	ENSP00000308895.4	P41440-1
SLC19A1	ENST00000567670.5	TSL:1	c.696T>G	p.Pro232Pro	synonymous	Exon 3 of 6	ENSP00000457278.1	H3BTQ3
SLC19A1	ENST00000380010.8	TSL:1	c.696T>G	p.Pro232Pro	synonymous	Exon 3 of 6	ENSP00000369347.4	P41440-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459860

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111752

Other (OTH)

AF:

0.00

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.36

(source)

DANN

Benign

0.34

PhyloP100

-6.6

PromoterAI

0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over