Variant X-78657726-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152694.3(RTL3):c.695A>C(p.Glu232Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,209,011 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 21 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000046 ( 0 hom. 17 hem. )

Consequence

RTL3
NM_152694.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.821

Variant links:

Genes affected

RTL3 (HGNC:22997): (retrotransposon Gag like 3) This gene is a member of a family of gag-related retrotransposon genes. These genes appear to have lost the ability to retrotranspose; however, their open reading frames have remained intact, which may indicate that these genes have acquired new functions in the cell. [provided by RefSeq, Nov 2009]

RTL3 links:

LOC107985670 (HGNC:):

LOC107985670 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007072538).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL3	NM_152694.3 link	c.695A>C	p.Glu232Ala	missense_variant	2/2	ENST00000321110.2	NP_689907.1	Q8N8U3
LOC107985670	XR_001755900.2 link	n.56+4212T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTL3	ENST00000321110.2 link	c.695A>C	p.Glu232Ala	missense_variant	2/2	2	NM_152694.3	ENSP00000316794.1		Q8N8U3

Frequencies

GnomAD3 genomes

AF:

0.0000720

AC:

AN:

111099

Hom.:

Cov.:

AF XY:

0.000150

AC XY:

AN XY:

33291

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00226

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000110

AC:

AN:

181650

Hom.:

AF XY:

0.0000905

AC XY:

AN XY:

66270

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00146

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000455

AC:

AN:

1097862

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

363238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00149

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000651

GnomAD4 genome

AF:

0.0000630

AC:

AN:

111149

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

33351

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00198

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000989

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.695A>C (p.E232A) alteration is located in exon 2 (coding exon 1) of the ZCCHC5 gene. This alteration results from a A to C substitution at nucleotide position 695, causing the glutamic acid (E) at amino acid position 232 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

0.11

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.012

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.28

M_CAP

Benign

0.011

MetaRNN

Benign

0.0071

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.2

REVEL

Benign

0.019

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.027

Polyphen

0.44

Vest4

0.038

MutPred

0.41

Loss of solvent accessibility (P = 0.0224);

MVP

0.21

MPC

0.0019

ClinPred

0.048

GERP RS

2.1

Varity_R

0.13

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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