10-98208893-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.779G>A(p.Ser260Asn) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: R3HCC1L NM_001351015.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0830

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]

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=0.06655902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HCC1L	NM_001351015.2	c.779G>A	p.Ser260Asn	missense_variant	5/10	ENST00000298999.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HCC1L	ENST00000298999.8	c.779G>A	p.Ser260Asn	missense_variant	5/10	5	NM_001351015.2	P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 20, 2023

The c.779G>A (p.S260N) alteration is located in exon 4 (coding exon 1) of the R3HCC1L gene. This alteration results from a G to A substitution at nucleotide position 779, causing the serine (S) at amino acid position 260 to be replaced by an asparagine (N). 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	0.099
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.45
Dann	Benign	0.76
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.033	N
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.067	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.75	N;N;.;.
REVEL	Benign	0.017
Sift	Benign	0.13	T;T;.;.
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.0030	.;.;B;.
Vest4		0.057
MutPred		0.23		Gain of sheet (P = 0.0011);Gain of sheet (P = 0.0011);Gain of sheet (P = 0.0011);Gain of sheet (P = 0.0011);
MVP		0.099
MPC		0.018
ClinPred		0.078	T
GERP RS		-3.3
Varity_R		0.018
gMVP		0.046

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: chr10-99968650;