Genetic Variant RC3H1:p.Thr906Ala (chr1-173947390-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_172071.4(RC3H1):c.2716A>G(p.Thr906Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,362 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: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RC3H1
NM_172071.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.15

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21337083).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RC3H1	NM_172071.4 link	c.2716A>G	p.Thr906Ala	missense_variant	Exon 15 of 20	ENST00000367696.7	NP_742068.1	Q5TC82-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RC3H1	ENST00000367696.7 link	c.2716A>G	p.Thr906Ala	missense_variant	Exon 15 of 20	5	NM_172071.4	ENSP00000356669.2	Q5TC82-1
RC3H1	ENST00000258349.8 link	c.2716A>G	p.Thr906Ala	missense_variant	Exon 14 of 19	1			Q5TC82-1
RC3H1	ENST00000367694.2 link	c.2716A>G	p.Thr906Ala	missense_variant	Exon 14 of 19	2		ENSP00000356667.2	Q5TC82-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251192

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461362

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 05, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2716A>G (p.T906A) alteration is located in exon 14 (coding exon 14) of the RC3H1 gene. This alteration results from a A to G substitution at nucleotide position 2716, causing the threonine (T) at amino acid position 906 to be replaced by an alanine (A). 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

0.057

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

T;T;.

Eigen

Benign

-0.092

Eigen_PC

Benign

0.042

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.66

T;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;M;M

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.051

Sift

Uncertain

0.0060

D;D;D

Sift4G

Benign

0.15

T;T;T

Polyphen

0.17

B;B;B

Vest4

0.39

MutPred

0.16

Loss of glycosylation at T906 (P = 0.0219);Loss of glycosylation at T906 (P = 0.0219);Loss of glycosylation at T906 (P = 0.0219);

MVP

0.50

MPC

0.29

ClinPred

0.57

GERP RS

5.5

Varity_R

0.12

gMVP

0.37

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over