11-72136069-C-A

Variant names:

• chr11-72136069-C-A
• rs377615092
• NM_000804.4:c.117C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N39N) has been classified as Likely benign.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2565736).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000804.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR3	NM_000804.4	MANE Select	c.117C>A	p.Asn39Lys	missense	Exon 2 of 5	NP_000795.2	P41439-1
	FOLR3	NR_178088.1		n.167C>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOLR3	ENST00000611028.3	TSL:1 MANE Select	c.117C>A	p.Asn39Lys	missense	Exon 2 of 5	ENSP00000481114.1	P41439-1
	FOLR3	ENST00000612844.4	TSL:1	n.117C>A		non_coding_transcript_exon	Exon 2 of 5	ENSP00000481027.1	P41439-4
	FOLR3	ENST00000897860.1		c.117C>A	p.Asn39Lys	missense	Exon 2 of 5	ENSP00000567919.1

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

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111918

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.90	T
PhyloP100		-1.7
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.11
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.054	T
Vest4		0.28
MutPred		0.51		Loss of ubiquitination at K41 (P = 0.037)
MVP		0.28
ClinPred		0.76	D
GERP RS		-7.6
PromoterAI		-0.018	Neutral
gMVP		0.45
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs377615092; hg19: chr11-71847115;