1-173943505-C-A

Variant names:

• chr1-173943505-C-A
• rs781513399
• NM_172071.4:c.3072G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_172071.4(RC3H1):​c.3072G>T​(p.Gln1024His) 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. 12/21 in silico tools predict 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: 3.17

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=0.41034886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RC3H1	NM_172071.4	c.3072G>T	p.Gln1024His	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.3072G>T	p.Gln1024His	missense_variant	Exon 18 of 20	5	NM_172071.4	ENSP00000356669.2
RC3H1	ENST00000258349.8	c.3072G>T	p.Gln1024His	missense_variant	Exon 17 of 19	1
RC3H1	ENST00000367694.2	c.3045G>T	p.Gln1015His	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

Feb 09, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3072G>T (p.Q1024H) alteration is located in exon 17 (coding exon 17) of the RC3H1 gene. This alteration results from a G to T substitution at nucleotide position 3072, causing the glutamine (Q) at amino acid position 1024 to be replaced by a histidine (H). 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	Benign	0.32
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T;T;.
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	T;.;D
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.41	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.46	T;T;T
Sift4G	Benign	0.24	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.71
MutPred		0.19		Gain of sheet (P = 0.1539);Gain of sheet (P = 0.1539);.;
MVP		0.46
MPC		0.98
ClinPred		0.95	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.19
gMVP		0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs781513399; hg19: chr1-173912643;