20-50592370-C-G

Position:

• chr20-50592370-C-G

Variant summary

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

The NM_001290268.2(RIPOR3):​c.2551G>C​(p.Val851Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000076 in 1,447,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000076 (0 hom.)
• Consequence: RIPOR3 NM_001290268.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.21

Genes affected

RIPOR3 (HGNC:16168): (RIPOR family member 3)

RIPOR3 (HGNC:):

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=0.15506905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR3	NM_001290268.2	c.2551G>C	p.Val851Leu	missense_variant	19/22	ENST00000327979.8	NP_001277197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPOR3	ENST00000327979.8	c.2551G>C	p.Val851Leu	missense_variant	19/22	2	NM_001290268.2	ENSP00000332663.3
RIPOR3	ENST00000045083.6	c.2539G>C	p.Val847Leu	missense_variant	19/22	5		ENSP00000045083.2
RIPOR3	ENST00000488529.5	n.874G>C		non_coding_transcript_exon_variant	6/7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000760 AC: 11 AN: 1447052 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 2 AN XY: 717780

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: 0.00000998

Gnomad4 OTH exome AF: 0.00

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

Aug 12, 2024

The c.2539G>C (p.V847L) alteration is located in exon 19 (coding exon 18) of the FAM65C gene. This alteration results from a G to C substitution at nucleotide position 2539, causing the valine (V) at amino acid position 847 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	0.18
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.041	T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.71	.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.75	T
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.18
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.038	B;B
Vest4		0.29
MVP		0.55
MPC		0.12
ClinPred		0.78	D
GERP RS		4.8
Varity_R		0.11
gMVP		0.23

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: chr20-49208907;