rs201535929

Variant names:

• chr20-50589730-C-A
• rs201535929
• NM_001290268.2:c.2617G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-50589730-C-A
• chr20-50589730-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001290268.2(RIPOR3):​c.2617G>T​(p.Ala873Ser) 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 1,461,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A873T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RIPOR3 NM_001290268.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.767
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061784893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR3	NM_001290268.2	c.2617G>T	p.Ala873Ser	missense_variant	Exon 20 of 22	ENST00000327979.8	NP_001277197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR3	ENST00000327979.8	c.2617G>T	p.Ala873Ser	missense_variant	Exon 20 of 22	2	NM_001290268.2	ENSP00000332663.3
RIPOR3	ENST00000045083.6	c.2605G>T	p.Ala869Ser	missense_variant	Exon 20 of 22	5		ENSP00000045083.2
RIPOR3	ENST00000462842.1	n.283G>T		non_coding_transcript_exon_variant	Exon 1 of 3	2
RIPOR3	ENST00000488529.5	n.940G>T		non_coding_transcript_exon_variant	Exon 7 of 7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461496 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727038

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111818

Other (OTH) AF: 0.00 AC: 0 AN: 60370

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.32
DANN	Benign	0.67
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.64	.;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.77
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.092
Sift	Benign	0.49	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.032	B;B
Vest4		0.18
MVP		0.31
MPC		0.11
ClinPred		0.31	T
GERP RS		0.79
Varity_R		0.041
gMVP		0.068
Mutation Taster		=96/4	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: rs201535929; hg19: chr20-49206267;