chr11-72136069-C-A

Variant names:

• chr11-72136069-C-A
• NM_000804.4:c.117C>A

Variant summary

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

The NM_000804.4(FOLR3):​c.117C>A​(p.Asn39Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FOLR3 NM_000804.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=0.2565736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOLR3	NM_000804.4	c.117C>A	p.Asn39Lys	missense_variant	Exon 2 of 5	ENST00000611028.3	NP_000795.2
FOLR3	NR_178088.1	n.167C>A		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOLR3	ENST00000611028.3	c.117C>A	p.Asn39Lys	missense_variant	Exon 2 of 5	1	NM_000804.4	ENSP00000481114.1
FOLR3	ENST00000612844.4	n.117C>A		non_coding_transcript_exon_variant	Exon 2 of 5	1		ENSP00000481027.1
FOLR3	ENST00000622388.4	c.117C>A	p.Asn39Lys	missense_variant	Exon 3 of 6	5		ENSP00000481833.1
FOLR3	ENST00000546166.1	c.111C>A	p.Asn37Lys	missense_variant	Exon 1 of 2	3		ENSP00000446279.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461764 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.0040
DANN	Benign	0.83
DEOGEN2	Benign	0.23	T;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.44	T;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.90	T
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.9	.;.;D;.
REVEL	Benign	0.11
Sift	Uncertain	0.027	.;.;D;.
Sift4G	Uncertain	0.054	T;D;T;T
Vest4		0.28, 0.28
MutPred		0.51		Loss of ubiquitination at K41 (P = 0.037);Loss of ubiquitination at K41 (P = 0.037);.;.;
MVP		0.28
ClinPred		0.76	D
GERP RS		-7.6
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-71847115;