rs1348055003

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004476.3(FOLH1):​c.2084G>C​(p.Ser695Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

FOLH1
NM_004476.3 missense

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00
Variant links:
Genes affected
FOLH1 (HGNC:3788): (folate hydrolase 1) This gene encodes a type II transmembrane glycoprotein belonging to the M28 peptidase family. The protein acts as a glutamate carboxypeptidase on different alternative substrates, including the nutrient folate and the neuropeptide N-acetyl-l-aspartyl-l-glutamate and is expressed in a number of tissues such as prostate, central and peripheral nervous system and kidney. A mutation in this gene may be associated with impaired intestinal absorption of dietary folates, resulting in low blood folate levels and consequent hyperhomocysteinemia. Expression of this protein in the brain may be involved in a number of pathological conditions associated with glutamate excitotoxicity. In the prostate the protein is up-regulated in cancerous cells and is used as an effective diagnostic and prognostic indicator of prostate cancer. This gene likely arose from a duplication event of a nearby chromosomal region. Alternative splicing gives rise to multiple transcript variants encoding several different isoforms. [provided by RefSeq, Jul 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3820646).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOLH1NM_004476.3 linkc.2084G>C p.Ser695Thr missense_variant Exon 19 of 19 ENST00000256999.7 NP_004467.1 Q04609-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOLH1ENST00000256999.7 linkc.2084G>C p.Ser695Thr missense_variant Exon 19 of 19 1 NM_004476.3 ENSP00000256999.2 Q04609-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
-0.083
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.33
T;.;.;.
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.93
D;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.38
T;T;T;T
MetaSVM
Benign
-0.84
T
MutationAssessor
Pathogenic
3.4
M;.;.;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.5
D;D;D;D
REVEL
Benign
0.20
Sift
Uncertain
0.0030
D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D
Polyphen
0.21
B;D;P;P
Vest4
0.46
MutPred
0.63
Gain of glycosylation at S695 (P = 0.0296);.;.;.;
MVP
0.53
MPC
1.8
ClinPred
0.98
D
GERP RS
2.3
Varity_R
0.58
gMVP
0.80

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.

Other links and lift over

dbSNP: rs1348055003; hg19: chr11-49168477; API