8-23291391-C-G

Variant names:

• chr8-23291391-C-G
• NM_001136108.3:c.883C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136108.3(R3HCC1):​c.883C>G​(p.Gln295Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: R3HCC1 NM_001136108.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.454
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.033343434).

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.883C>G	p.Gln295Glu	missense	Exon 5 of 8	NP_001129580.2	Q9Y3T6-1
	R3HCC1	NM_001301650.2		c.757C>G	p.Gln253Glu	missense	Exon 6 of 9	NP_001288579.1	Q9Y3T6-3
	R3HCC1	NR_125897.1		n.852C>G		non_coding_transcript_exon	Exon 6 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HCC1	ENST00000265806.12	TSL:1 MANE Select	c.883C>G	p.Gln295Glu	missense	Exon 5 of 8	ENSP00000265806.8	Q9Y3T6-1
	R3HCC1	ENST00000625275.3	TSL:1	c.757C>G	p.Gln253Glu	missense	Exon 6 of 9	ENSP00000486278.2	Q9Y3T6-3
	R3HCC1	ENST00000522012.6	TSL:1	n.*162C>G		non_coding_transcript_exon	Exon 6 of 9	ENSP00000487121.2	A0A0D9SG39

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1399456 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690228

African (AFR) AF: 0.0000316 AC: 1 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5690

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078902

Other (OTH) AF: 0.00 AC: 0 AN: 58042

GnomAD4 genome Cov.: 33

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	0.062
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.61
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.45
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.029
Sift	Benign	0.47	T
Sift4G	Benign	0.66	T
Vest4		0.050
MutPred		0.21		Gain of disorder (P = 0.0637)
MVP		0.067
ClinPred		0.050	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.17
Mutation Taster		=91/9	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

hg19: chr8-23148904;