chrX-78657381-G-A

Variant summary

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

The NM_152694.3(RTL3):​c.1040C>T​(p.Ala347Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,210,348 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0000089 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

RTL3
NM_152694.3 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.542
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 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=0.1383731).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RTL3NM_152694.3 linkc.1040C>T p.Ala347Val missense_variant 2/2 ENST00000321110.2 NP_689907.1 Q8N8U3
LOC107985670XR_001755900.2 linkn.56+3867G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RTL3ENST00000321110.2 linkc.1040C>T p.Ala347Val missense_variant 2/22 NM_152694.3 ENSP00000316794.1 Q8N8U3

Frequencies

GnomAD3 genomes
AF:
0.00000891
AC:
1
AN:
112193
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34339
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000546
AC:
1
AN:
183082
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67586
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:
0.0000122
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
9.11e-7
AC:
1
AN:
1098155
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
1
AN XY:
363523
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:
0.00000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000891
AC:
1
AN:
112193
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34339
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000149
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

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 GeneticsMar 18, 2024The c.1040C>T (p.A347V) alteration is located in exon 2 (coding exon 1) of the ZCCHC5 gene. This alteration results from a C to T substitution at nucleotide position 1040, causing the alanine (A) at amino acid position 347 to be replaced by a valine (V). 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
0.15
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
7.0
DANN
Benign
0.89
DEOGEN2
Benign
0.14
T
FATHMM_MKL
Benign
0.21
N
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.34
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.071
Sift
Benign
0.12
T
Sift4G
Benign
0.20
T
Polyphen
0.0010
B
Vest4
0.22
MVP
0.42
MPC
0.0014
ClinPred
0.081
T
GERP RS
-0.58
Varity_R
0.094
gMVP
0.34

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: rs148353898; hg19: chrX-77912878; API