Variant chr4-75490616-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_015436.4(RCHY1):c.622C>G(p.Pro208Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,612,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

RCHY1
NM_015436.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

Variant links:

Genes affected

RCHY1 (HGNC:17479): (ring finger and CHY zinc finger domain containing 1) The protein encoded by this gene has ubiquitin ligase activity. It mediates E3-dependent ubiquitination and proteasomal degradation of target proteins, including tumor protein 53, histone deacetylase 1, and cyclin-dependent kinase inhibitor 1B, thus regulating their levels and cell cycle progression. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2013]

RCHY1 links:

RCHY1 (HGNC:):

RCHY1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28722197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCHY1	NM_015436.4 linkuse as main transcript	c.622C>G	p.Pro208Ala	missense_variant	8/9	ENST00000324439.10	NP_056251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCHY1	ENST00000324439.10 linkuse as main transcript	c.622C>G	p.Pro208Ala	missense_variant	8/9	1	NM_015436.4	ENSP00000321239.5		Q96PM5-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1460284

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726548

show subpopulations

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:

0.0000225

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2024

The c.622C>G (p.P208A) alteration is located in exon 8 (coding exon 8) of the RCHY1 gene. This alteration results from a C to G substitution at nucleotide position 622, causing the proline (P) at amino acid position 208 to be replaced by an alanine (A). 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

0.14

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.70

D;.;.;.;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

D;D;D;T;D

M_CAP

Benign

0.0078

MetaRNN

Benign

0.29

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.8

M;.;.;.;.

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-6.0

D;D;D;D;D

REVEL

Benign

0.26

Sift

Benign

0.17

T;T;T;T;D

Sift4G

Benign

0.084

T;D;T;D;D

Polyphen

1.0

D;.;.;D;.

Vest4

0.38

MutPred

0.39

Gain of helix (P = 0.0425);.;.;.;.;

MVP

0.20

MPC

0.56

ClinPred

0.97

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over