Variant 10-98208684-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001351015.2(R3HCC1L):c.570G>T(p.Arg190Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

R3HCC1L
NM_001351015.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.402

Variant links:

Genes affected

R3HCC1L (HGNC:23512): (R3H domain and coiled-coil containing 1 like) Colocalizes with exon-exon junction complex. [provided by Alliance of Genome Resources, Apr 2022]

R3HCC1L links:

R3HCC1L (HGNC:):

R3HCC1L links:

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ACMG classification

Classification made for transcript

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=0.09956211).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HCC1L	NM_001351015.2 linkuse as main transcript	c.570G>T	p.Arg190Ser	missense_variant	5/10	ENST00000298999.8	NP_001337944.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HCC1L	ENST00000298999.8 linkuse as main transcript	c.570G>T	p.Arg190Ser	missense_variant	5/10	5	NM_001351015.2	ENSP00000298999.3		A0A384DVK4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250970

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 13, 2023

The c.570G>T (p.R190S) alteration is located in exon 4 (coding exon 1) of the R3HCC1L gene. This alteration results from a G to T substitution at nucleotide position 570, causing the arginine (R) at amino acid position 190 to be replaced by a serine (S). 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

-0.39

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.7

DANN

Benign

0.86

DEOGEN2

Benign

0.011

.;.;T;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.64

.;.;T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

.;.;M;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.5

N;N;.;.

REVEL

Benign

0.025

Sift

Uncertain

0.0070

D;D;.;.

Sift4G

Uncertain

0.059

T;T;T;T

Polyphen

0.76

.;.;P;.

Vest4

0.27

MutPred

0.26

Gain of glycosylation at R190 (P = 0.022);Gain of glycosylation at R190 (P = 0.022);Gain of glycosylation at R190 (P = 0.022);Gain of glycosylation at R190 (P = 0.022);

MVP

0.22

MPC

0.083

ClinPred

0.13

GERP RS

-0.0017

Varity_R

0.081

gMVP

0.033

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

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