chr1-173943468-C-T

Variant names:

• chr1-173943468-C-T
• rs765577379
• NM_172071.4:c.3109G>A

Variant summary

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

The NM_172071.4(RC3H1):​c.3109G>A​(p.Gly1037Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RC3H1 NM_172071.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81
• Publications: 0 publications found

Genes affected

RC3H1 (HGNC:29434): (ring finger and CCCH-type domains 1) This gene encodes a protein containing RING-type and C3H1-type zinc finger motifs. The encoded protein recognizes and binds to a constitutive decay element (CDE) in the 3' UTR of mRNAs, leading to mRNA deadenylation and degradation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

RC3H1 Gene-Disease associations (from GenCC):

• hemophagocytic lymphohistiocytosis, familial, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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=0.40095115).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172071.4. 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
	RC3H1	NM_172071.4	MANE Select	c.3109G>A	p.Gly1037Arg	missense	Exon 18 of 20	NP_742068.1	Q5TC82-1
	RC3H1	NM_001300850.1		c.3109G>A	p.Gly1037Arg	missense	Exon 17 of 19	NP_001287779.1	B9EGU6
	RC3H1	NM_001300851.1		c.3082G>A	p.Gly1028Arg	missense	Exon 17 of 19	NP_001287780.1	Q5TC82-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RC3H1	ENST00000367696.7	TSL:5 MANE Select	c.3109G>A	p.Gly1037Arg	missense	Exon 18 of 20	ENSP00000356669.2	Q5TC82-1
	RC3H1	ENST00000892872.1		c.3109G>A	p.Gly1037Arg	missense	Exon 17 of 19	ENSP00000562931.1
	RC3H1	ENST00000367694.2	TSL:2	c.3082G>A	p.Gly1028Arg	missense	Exon 17 of 19	ENSP00000356667.2	Q5TC82-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Uncertain	0.55
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.13	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		5.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Uncertain	0.019	D
Sift4G	Benign	0.30	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.16		Gain of MoRF binding (P = 0.0116)
MVP		0.26
MPC		1.1
ClinPred		0.98	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.39
gMVP		0.48
Mutation Taster		=74/26	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs765577379; hg19: chr1-173912606;