rs771023021

Variant summary

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

The NM_004476.3(FOLH1):​c.2053C>T​(p.Pro685Ser) 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)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

FOLH1
NM_004476.3 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81
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]

Genome browser will be placed here

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=0.35952118).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOLH1NM_004476.3 linkc.2053C>T p.Pro685Ser missense_variant Exon 18 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.2053C>T p.Pro685Ser missense_variant Exon 18 of 19 1 NM_004476.3 ENSP00000256999.2 Q04609-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000126
AC:
3
AN:
238118
Hom.:
0
AF XY:
0.00000776
AC XY:
1
AN XY:
128874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000985
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000208
AC:
3
AN:
1443428
Hom.:
0
Cov.:
29
AF XY:
0.00000139
AC XY:
1
AN XY:
717908
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000739
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.31
T;.
Eigen
Benign
-0.033
Eigen_PC
Benign
0.035
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.36
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-4.0
D;D
REVEL
Benign
0.074
Sift
Benign
0.057
T;T
Sift4G
Benign
0.24
T;T
Polyphen
0.13
B;B
Vest4
0.29
MutPred
0.41
Gain of phosphorylation at P685 (P = 0.0641);.;
MVP
0.57
MPC
1.4
ClinPred
0.87
D
GERP RS
3.6
Varity_R
0.51
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs771023021; hg19: chr11-49170201; API