8-23290051-G-C

Variant names:

• chr8-23290051-G-C
• rs3808536
• NM_001136108.3:c.434G>C

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.434G>C​(p.Arg145Thr) 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. 11/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: R3HCC1 NM_001136108.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 23 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 (REVEL=0.07).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HCC1	NM_001136108.3	MANE Select	c.434G>C	p.Arg145Thr	missense	Exon 4 of 8	NP_001129580.2
	R3HCC1	NR_125897.1		n.518G>C		non_coding_transcript_exon	Exon 4 of 9
	R3HCC1	NM_001301650.2		c.309-1G>C		splice_acceptor intron	N/A	NP_001288579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HCC1	ENST00000265806.12	TSL:1 MANE Select	c.434G>C	p.Arg145Thr	missense	Exon 4 of 8	ENSP00000265806.8
	R3HCC1	ENST00000522012.6	TSL:1	n.434G>C		non_coding_transcript_exon	Exon 4 of 9	ENSP00000487121.2
	R3HCC1	ENST00000625275.3	TSL:1	c.309-1G>C		splice_acceptor intron	N/A	ENSP00000486278.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.91
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.37	N
M_CAP	Benign	0.022	T
PhyloP100		0.36
ClinPred		0.14	T
GERP RS		2.5
PromoterAI		0.010	Neutral
Mutation Taster		=68/32	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3808536; hg19: chr8-23147564;