10-98208344-G-A

Position:

• chr10-98208344-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001351015.2(R3HCC1L):​c.230G>A​(p.Arg77Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: R3HCC1L NM_001351015.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.461

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035280794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
R3HCC1L	NM_001351015.2	c.230G>A	p.Arg77Lys	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	c.230G>A	p.Arg77Lys	missense_variant	5/10	5	NM_001351015.2	ENSP00000298999.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 02, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.2
DANN	Benign	0.63
DEOGEN2	Benign	0.0016	.;.;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.55	.;.;T;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.035	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.13	.;.;N;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.39	N;N;.;.
REVEL	Benign	0.048
Sift	Benign	0.54	T;T;.;.
Sift4G	Benign	0.68	T;T;T;T
Polyphen		0.0040	.;.;B;.
Vest4		0.033
MutPred		0.16		Gain of ubiquitination at R77 (P = 0.0077);Gain of ubiquitination at R77 (P = 0.0077);Gain of ubiquitination at R77 (P = 0.0077);Gain of ubiquitination at R77 (P = 0.0077);
MVP		0.17
MPC		0.018
ClinPred		0.022	T
GERP RS		0.16
Varity_R		0.029
gMVP		0.011

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: chr10-99968101;