rs58836581

Variant names:

• chr21-45515870-C-A
• rs58836581
• NM_194255.4:c.1564G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-45515870-C-A
• chr21-45515870-C-G
• chr21-45515870-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194255.4(SLC19A1):​c.1564G>T​(p.Asp522Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000035 in 1,428,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. D522N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SLC19A1 NM_194255.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17487839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.1564G>T	p.Asp522Tyr	missense_variant	Exon 6 of 6	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9	c.1564G>T	p.Asp522Tyr	missense_variant	Exon 6 of 6	1	NM_194255.4	ENSP00000308895.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000350 AC: 5 AN: 1428070 Hom.: 0 Cov.: 36 AF XY: 0.00000424 AC XY: 3 AN XY: 707000

African (AFR) AF: 0.00 AC: 0 AN: 32728

American (AMR) AF: 0.00 AC: 0 AN: 40316

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24030

East Asian (EAS) AF: 0.00 AC: 0 AN: 39064

South Asian (SAS) AF: 0.00 AC: 0 AN: 81890

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5622

European-Non Finnish (NFE) AF: 0.00000457 AC: 5 AN: 1094498

Other (OTH) AF: 0.00 AC: 0 AN: 58794

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.044	T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;.
PhyloP100		1.4
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.0080	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;.
Vest4		0.26
MutPred		0.14		Gain of catalytic residue at D522 (P = 0.0193);.;
MVP		0.44
MPC		0.56
ClinPred		0.56	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.14
gMVP		0.23
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs58836581; hg19: chr21-46935784;