chrX-78657184-C-T

Variant summary

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

The NM_152694.3(RTL3):​c.1237G>A​(p.Glu413Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,210,789 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.000025 ( 0 hom. 8 hem. )

Consequence

RTL3
NM_152694.3 missense

Scores

16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.876
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]

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=0.04146731).
BS2
High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RTL3NM_152694.3 linkc.1237G>A p.Glu413Lys missense_variant 2/2 ENST00000321110.2 NP_689907.1 Q8N8U3
LOC107985670XR_001755900.2 linkn.56+3670C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RTL3ENST00000321110.2 linkc.1237G>A p.Glu413Lys missense_variant 2/22 NM_152694.3 ENSP00000316794.1 Q8N8U3

Frequencies

GnomAD3 genomes
AF:
0.0000266
AC:
3
AN:
112576
Hom.:
0
Cov.:
23
AF XY:
0.0000576
AC XY:
2
AN XY:
34728
show subpopulations
Gnomad AFR
AF:
0.0000646
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000368
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000545
AC:
10
AN:
183329
Hom.:
0
AF XY:
0.0000147
AC XY:
1
AN XY:
67801
show subpopulations
Gnomad AFR exome
AF:
0.000456
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:
0.0000367
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000255
AC:
28
AN:
1098213
Hom.:
0
Cov.:
31
AF XY:
0.0000220
AC XY:
8
AN XY:
363579
show subpopulations
Gnomad4 AFR exome
AF:
0.000265
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:
0.0000249
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000266
AC:
3
AN:
112576
Hom.:
0
Cov.:
23
AF XY:
0.0000576
AC XY:
2
AN XY:
34728
show subpopulations
Gnomad4 AFR
AF:
0.0000646
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000368
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000680
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00104
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsNov 21, 2024The c.1237G>A (p.E413K) alteration is located in exon 2 (coding exon 1) of the ZCCHC5 gene. This alteration results from a G to A substitution at nucleotide position 1237, causing the glutamic acid (E) at amino acid position 413 to be replaced by a lysine (K). 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
0.076
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.78
CADD
Benign
8.6
DANN
Benign
0.84
DEOGEN2
Benign
0.0033
T
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.041
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-0.86
N
REVEL
Benign
0.026
Sift
Benign
0.27
T
Sift4G
Benign
0.32
T
Polyphen
0.58
P
Vest4
0.068
MVP
0.030
MPC
0.0013
ClinPred
0.015
T
GERP RS
2.2
Varity_R
0.13
gMVP
0.19

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.

Other links and lift over

dbSNP: rs143363623; hg19: chrX-77912681; COSMIC: COSV58186182; API