rs1168676375

Variant names:

• chr8-23294786-C-G
• rs1168676375
• NM_001136108.3:c.1114C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-23294786-C-G
• chr8-23294786-C-T
• chr8-23294786-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136108.3(R3HCC1):​c.1114C>G​(p.Arg372Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,551,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R372W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: R3HCC1 NM_001136108.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.49
• Publications: 1 publications found

Genes affected

R3HCC1 (HGNC:27329): (R3H domain and coiled-coil containing 1) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.157801).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136108.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HCC1	NM_001136108.3	MANE Select	c.1114C>G	p.Arg372Gly	missense	Exon 7 of 8	NP_001129580.2	Q9Y3T6-1
	R3HCC1	NM_001301650.2		c.988C>G	p.Arg330Gly	missense	Exon 8 of 9	NP_001288579.1	Q9Y3T6-3
	R3HCC1	NR_125897.1		n.1083C>G		non_coding_transcript_exon	Exon 8 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HCC1	ENST00000265806.12	TSL:1 MANE Select	c.1114C>G	p.Arg372Gly	missense	Exon 7 of 8	ENSP00000265806.8	Q9Y3T6-1
	R3HCC1	ENST00000625275.3	TSL:1	c.988C>G	p.Arg330Gly	missense	Exon 8 of 9	ENSP00000486278.2	Q9Y3T6-3
	R3HCC1	ENST00000522012.6	TSL:1	n.*393C>G		non_coding_transcript_exon	Exon 8 of 9	ENSP00000487121.2	A0A0D9SG39

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152022 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399080 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690040

African (AFR) AF: 0.00 AC: 0 AN: 31596

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35736

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078914

Other (OTH) AF: 0.0000172 AC: 1 AN: 57990

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152022 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74258

African (AFR) AF: 0.00 AC: 0 AN: 41384

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
PhyloP100		1.5
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.12
Sift	Benign	0.25	T
Sift4G	Benign	0.16	T
Vest4		0.38
MutPred		0.33		Loss of solvent accessibility (P = 0.0329)
MVP		0.22
ClinPred		0.98	D
GERP RS		4.6
gMVP		0.43
Mutation Taster		=88/12	polymorphism

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: rs1168676375; hg19: chr8-23152299;