chr11-72139101-C-A

Variant names:

• chr11-72139101-C-A
• rs564543390
• NM_000804.4:c.309C>A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_000804.4(FOLR3):​c.309C>A​(p.Asp103Glu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 28)
• Consequence: FOLR3 NM_000804.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a binding_site (size 0) in uniprot entity FOLR3_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLR3	NM_000804.4	c.309C>A	p.Asp103Glu	missense_variant	Exon 3 of 5	ENST00000611028.3	NP_000795.2
FOLR3	NR_178088.1	n.487C>A		non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLR3	ENST00000611028.3	c.309C>A	p.Asp103Glu	missense_variant	Exon 3 of 5	1	NM_000804.4	ENSP00000481114.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.040	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	12
DANN	Benign	0.96
DEOGEN2	Benign	0.24	T;.;.
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-0.73	T
PrimateAI	Uncertain	0.60	T
REVEL	Uncertain	0.50
Sift4G	Benign	0.13	T;T;T
Vest4		0.86, 0.85
MutPred		0.65		.;.;Loss of catalytic residue at D101 (P = 0.3569);
MVP		0.29
ClinPred		0.99	D
GERP RS		1.3
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs564543390; hg19: chr11-71850147;