20-50587259-C-G

Position:

• chr20-50587259-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.2826G>C​(p.Glu942Asp) 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 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RIPOR3 NM_001290268.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.206

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=0.090693295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPOR3	NM_001290268.2	c.2826G>C	p.Glu942Asp	missense_variant	22/22	ENST00000327979.8	NP_001277197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPOR3	ENST00000327979.8	c.2826G>C	p.Glu942Asp	missense_variant	22/22	2	NM_001290268.2	ENSP00000332663.3
RIPOR3	ENST00000045083.6	c.2814G>C	p.Glu938Asp	missense_variant	22/22	5		ENSP00000045083.2
RIPOR3	ENST00000462842.1	n.492G>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461828 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727224

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.: 33

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

Oct 03, 2024

The c.2814G>C (p.E938D) alteration is located in exon 22 (coding exon 21) of the FAM65C gene. This alteration results from a G to C substitution at nucleotide position 2814, causing the glutamic acid (E) at amino acid position 938 to be replaced by an aspartic acid (D). 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	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.63	.;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-0.79	T
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.88	N;N
REVEL	Benign	0.14
Sift	Benign	0.13	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.49	P;P
Vest4		0.11
MVP		0.39
MPC		0.13
ClinPred		0.18	T
GERP RS		-0.98
Varity_R		0.067
gMVP		0.18

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: chr20-49203796;