11-72135971-A-T

Position:

• chr11-72135971-A-T

Variant summary

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

The NM_000804.4(FOLR3):​c.19A>T​(p.Met7Leu) 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. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FOLR3 NM_000804.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.229

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08722988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOLR3	NM_000804.4	c.19A>T	p.Met7Leu	missense_variant	2/5	ENST00000611028.3	NP_000795.2
FOLR3	NR_178088.1	n.69A>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FOLR3	ENST00000611028.3	c.19A>T	p.Met7Leu	missense_variant	2/5	1	NM_000804.4	ENSP00000481114	P1
FOLR3	ENST00000612844.4	c.19A>T	p.Met7Leu	missense_variant, NMD_transcript_variant	2/5	1		ENSP00000481027
FOLR3	ENST00000622388.4	c.19A>T	p.Met7Leu	missense_variant	3/6	5		ENSP00000481833
FOLR3	ENST00000546166.1	c.13A>T	p.Met5Leu	missense_variant	1/2	3		ENSP00000446279

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.19A>T (p.M7L) alteration is located in exon 2 (coding exon 1) of the FOLR3 gene. This alteration results from a A to T substitution at nucleotide position 19, causing the methionine (M) at amino acid position 7 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.37
DANN	Benign	0.62
DEOGEN2	Benign	0.039	T;.;T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.11	T;T;T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.087	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.76	.;.;N;.
REVEL	Benign	0.17
Sift	Benign	1.0	.;.;T;.
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.12, 0.15
MutPred		0.56		Loss of disorder (P = 0.0824);Loss of disorder (P = 0.0824);.;.;
MVP		0.12
ClinPred		0.054	T
GERP RS		-6.6
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-71847017;