rs11189513

Variant names:

• chr10-98209811-A-G
• rs11189513
• NM_001351015.2:c.1697A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-98209811-A-G
• chr10-98209811-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351015.2(R3HCC1L):​c.1697A>G​(p.His566Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,613,216 control chromosomes in the GnomAD database, including 83,396 homozygotes. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H566Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.27 (6264 hom., cov: 32)
  • Exomes 𝑓: 0.32 (77132 hom.)
• Consequence: R3HCC1L NM_001351015.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 37 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.4430623E-4).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
R3HCC1L	NM_001351015.2	c.1697A>G	p.His566Arg	missense_variant	Exon 5 of 10	ENST00000298999.8	NP_001337944.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HCC1L	ENST00000298999.8	c.1697A>G	p.His566Arg	missense_variant	Exon 5 of 10	5	NM_001351015.2	ENSP00000298999.3

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41049 AN: 151908 Hom.: 6267 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.274

GnomAD2 exomes AF: 0.328 AC: 82457 AN: 251024 AF XY: 0.334

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.417

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.322

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.326

GnomAD4 exome AF: 0.320 AC: 468214 AN: 1461190 Hom.: 77132 Cov.: 41 AF XY: 0.324 AC XY: 235170 AN XY: 726902

African (AFR) AF: 0.114 AC: 3806 AN: 33452

American (AMR) AF: 0.410 AC: 18341 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 7660 AN: 26120

East Asian (EAS) AF: 0.269 AC: 10675 AN: 39690

South Asian (SAS) AF: 0.424 AC: 36540 AN: 86210

European-Finnish (FIN) AF: 0.307 AC: 16419 AN: 53408

Middle Eastern (MID) AF: 0.318 AC: 1835 AN: 5764

European-Non Finnish (NFE) AF: 0.318 AC: 353877 AN: 1111458

Other (OTH) AF: 0.316 AC: 19061 AN: 60378

GnomAD4 genome AF: 0.270 AC: 41054 AN: 152026 Hom.: 6264 Cov.: 32 AF XY: 0.273 AC XY: 20275 AN XY: 74288

African (AFR) AF: 0.121 AC: 5029 AN: 41502

American (AMR) AF: 0.357 AC: 5447 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1606 AN: 5172

South Asian (SAS) AF: 0.423 AC: 2039 AN: 4820

European-Finnish (FIN) AF: 0.313 AC: 3303 AN: 10556

Middle Eastern (MID) AF: 0.266 AC: 77 AN: 290

European-Non Finnish (NFE) AF: 0.320 AC: 21743 AN: 67938

Other (OTH) AF: 0.271 AC: 572 AN: 2108

Alfa AF: 0.300 Hom.: 23888

Bravo AF: 0.264

TwinsUK AF: 0.309 AC: 1145

ALSPAC AF: 0.322 AC: 1242

ESP6500AA AF: 0.127 AC: 559

ESP6500EA AF: 0.301 AC: 2591

ExAC AF: 0.322 AC: 39104

Asia WGS AF: 0.350 AC: 1218 AN: 3478

EpiCase AF: 0.317

EpiControl AF: 0.310

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.64
DEOGEN2	Benign	0.0035	.;.;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.37	.;.;T;T
MetaRNN	Benign	0.00034	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.1	.;.;L;.
PhyloP100		-0.025
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N;N;.;.
REVEL	Benign	0.021
Sift	Benign	0.15	T;T;.;.
Sift4G	Benign	0.55	T;T;T;T
Polyphen		0.010	.;.;B;.
Vest4		0.030
MPC		0.018
ClinPred		0.014	T
GERP RS		-2.0
Varity_R		0.045
gMVP		0.035
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11189513; hg19: chr10-99969568; COSMIC: COSV54401406;