chr21-45515761-G-A

Position:

• chr21-45515761-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_194255.4(SLC19A1):​c.1673C>T​(p.Ala558Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency: Genomes: not found (cov: 34)
• Consequence: SLC19A1 NM_194255.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078543514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.1673C>T	p.Ala558Val	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	c.1673C>T	p.Ala558Val	missense_variant	6/6	1	NM_194255.4	ENSP00000308895.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.39
DANN	Benign	0.91
DEOGEN2	Benign	0.032	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.41	T;T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.014	D;D
Polyphen		0.0010	B;.
Vest4		0.031
MutPred		0.044		Loss of helix (P = 0.1299);.;
MVP		0.50
MPC		0.12
ClinPred		0.069	T
GERP RS		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.052
gMVP		0.076

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

Other links and lift over

dbSNP: rs35786590; hg19: chr21-46935675;