rs1802914516

Variant names:

• chr8-23293346-C-T
• rs1802914516
• NM_001136108.3:c.1069C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001136108.3(R3HCC1):​c.1069C>T​(p.Leu357Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: R3HCC1 NM_001136108.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.21
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36438113).

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.1069C>T	p.Leu357Phe	missense	Exon 6 of 8	NP_001129580.2	Q9Y3T6-1
	R3HCC1	NM_001301650.2		c.943C>T	p.Leu315Phe	missense	Exon 7 of 9	NP_001288579.1	Q9Y3T6-3
	R3HCC1	NR_125897.1		n.1038C>T		non_coding_transcript_exon	Exon 7 of 9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HCC1	ENST00000265806.12	TSL:1 MANE Select	c.1069C>T	p.Leu357Phe	missense	Exon 6 of 8	ENSP00000265806.8	Q9Y3T6-1
	R3HCC1	ENST00000625275.3	TSL:1	c.943C>T	p.Leu315Phe	missense	Exon 7 of 9	ENSP00000486278.2	Q9Y3T6-3
	R3HCC1	ENST00000522012.6	TSL:1	n.*348C>T		non_coding_transcript_exon	Exon 7 of 9	ENSP00000487121.2	A0A0D9SG39

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74336

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.64
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.78	T
PhyloP100		2.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Vest4		0.66
MutPred		0.43		Gain of loop (P = 0.2045)
MVP		0.088
ClinPred		0.98	D
GERP RS		3.0
gMVP		0.44
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1802914516; hg19: chr8-23150859;