10-98208928-A-G

Variant summary

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

The NM_001351015.2(R3HCC1L):c.814A>G(p.Ser272Gly) 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: 1.20

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 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=0.088171154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
R3HCC1L	NM_001351015.2	c.814A>G	p.Ser272Gly	missense_variant	5/10	ENST00000298999.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
R3HCC1L	ENST00000298999.8	c.814A>G	p.Ser272Gly	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

Oct 25, 2023

The c.814A>G (p.S272G) alteration is located in exon 4 (coding exon 1) of the R3HCC1L gene. This alteration results from a A to G substitution at nucleotide position 814, causing the serine (S) at amino acid position 272 to be replaced by a glycine (G). 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	0.094
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	7.9
Dann	Benign	0.95
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.088	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.2	N;N;.;.
REVEL	Benign	0.026
Sift	Benign	0.30	T;T;.;.
Sift4G	Benign	0.50	T;T;T;T
Polyphen		0.0	.;.;B;.
Vest4		0.073
MutPred		0.17		Loss of glycosylation at S272 (P = 0.0033);Loss of glycosylation at S272 (P = 0.0033);Loss of glycosylation at S272 (P = 0.0033);Loss of glycosylation at S272 (P = 0.0033);
MVP		0.28
MPC		0.017
ClinPred		0.040	T
GERP RS		3.2
Varity_R		0.032
gMVP		0.086

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: chr10-99968685;