1-173943468-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40095115).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RC3H1	NM_172071.4	c.3109G>A	p.Gly1037Arg	missense_variant	Exon 18 of 20	ENST00000367696.7	NP_742068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RC3H1	ENST00000367696.7	c.3109G>A	p.Gly1037Arg	missense_variant	Exon 18 of 20	5	NM_172071.4	ENSP00000356669.2
RC3H1	ENST00000258349.8	c.3109G>A	p.Gly1037Arg	missense_variant	Exon 17 of 19	1
RC3H1	ENST00000367694.2	c.3082G>A	p.Gly1028Arg	missense_variant	Exon 17 of 19	2		ENSP00000356667.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3109G>A (p.G1037R) alteration is located in exon 17 (coding exon 17) of the RC3H1 gene. This alteration results from a G to A substitution at nucleotide position 3109, causing the glycine (G) at amino acid position 1037 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;.;D
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M;M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.019	D;D;D
Sift4G	Benign	0.30	T;T;D
Polyphen		1.0	D;D;D
Vest4		0.66
MutPred		0.16		Gain of MoRF binding (P = 0.0116);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-173912606;