rs34016544

Variant names:

• chr6-24843512-C-G
• NM_001286445.3:c.1207G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-24843512-C-G
• chr6-24843512-C-T

Variant summary

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

The NM_001286445.3(RIPOR2):​c.1207G>C​(p.Glu403Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000722 in 1,385,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: RIPOR2 NM_001286445.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59

Genes affected

RIPOR2 (HGNC:13872): (RHO family interacting cell polarization regulator 2) This gene encodes an atypical inhibitor of the small G protein RhoA. Inhibition of RhoA activity by the encoded protein mediates myoblast fusion and polarization of T cells and neutrophils. The encoded protein is a component of hair cell stereocilia that is essential for hearing. A splice site mutation in this gene results in hearing loss in human patients. [provided by RefSeq, Sep 2016]

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=0.14303014).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPOR2	NM_001286445.3	c.1207G>C	p.Glu403Gln	missense_variant	Exon 13 of 22	ENST00000643898.2	NP_001273374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPOR2	ENST00000643898.2	c.1207G>C	p.Glu403Gln	missense_variant	Exon 13 of 22		NM_001286445.3	ENSP00000494268.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.22e-7 AC: 1 AN: 1385670 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 680674

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: 9.32e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T;T;T;.;.;.;T;.;.;.;.;.;.
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.92	.;D;.;D;D;.;D;D;.;D;D;.;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.53	.;.;N;.;.;N;N;N;.;.;.;.;.
REVEL	Benign	0.11
Sift	Benign	0.18	.;.;T;.;.;T;T;T;.;.;.;.;.
Sift4G	Benign	0.33	.;T;T;.;.;T;T;T;.;.;.;.;.
Polyphen		0.085	B;B;B;.;.;P;P;.;P;P;.;.;.
Vest4		0.066, 0.073, 0.078, 0.087, 0.076
MutPred		0.12		Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;.;.;.;.;.;.;.;.;Gain of helix (P = 0.132);
MVP		0.35
MPC		0.30
ClinPred		0.47	T
GERP RS		3.9
Varity_R		0.052
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-24843740;