Genetic Variant NM_000804.4:c.82C>T (chr11-72136034-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_000804.4(FOLR3):c.82C>T(p.Arg28Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,613,718 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

FOLR3
NM_000804.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Variant links:

Genes affected

FOLR3 (HGNC:3795): (folate receptor gamma) This gene encodes a member of the folate receptor (FOLR) family of proteins, which have a high affinity for folic acid and for several reduced folic acid derivatives, and mediate delivery of 5-methyltetrahydrofolate to the interior of cells. Expression of this gene may be elevated in ovarian and primary peritoneal carcinoma. This gene is present in a gene cluster on chromosome 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

FOLR3 links:

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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=0.3268962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLR3	NM_000804.4 link	c.82C>T	p.Arg28Trp	missense_variant	Exon 2 of 5	ENST00000611028.3	NP_000795.2	P41439-1
FOLR3	NR_178088.1 link	n.132C>T		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOLR3	ENST00000611028.3 link	c.82C>T	p.Arg28Trp	missense_variant	Exon 2 of 5	1	NM_000804.4	ENSP00000481114.1	P41439-1
FOLR3	ENST00000612844.4 link	n.82C>T		non_coding_transcript_exon_variant	Exon 2 of 5	1		ENSP00000481027.1	P41439-4
FOLR3	ENST00000622388.4 link	c.82C>T	p.Arg28Trp	missense_variant	Exon 3 of 6	5		ENSP00000481833.1	A0A087WYI3
FOLR3	ENST00000546166.1 link	c.76C>T	p.Arg26Trp	missense_variant	Exon 1 of 2	3		ENSP00000446279.1	F5H2G8

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250280

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135450

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000287

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000315

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152026

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.3

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

T;.;T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Benign

-0.85

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.41

.;.;N;.

REVEL

Benign

0.17

Sift

Benign

0.11

.;.;T;.

Sift4G

Benign

0.086

T;T;T;T

Vest4

0.12, 0.14

MutPred

0.67

Loss of disorder (P = 0.0045);Loss of disorder (P = 0.0045);.;.;

MVP

0.63

ClinPred

0.52

GERP RS

-2.1

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over