Variant X-112455276-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001395362.2(RTL4):c.548A>C(p.Gln183Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000389 in 1,209,571 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 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 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000041 ( 0 hom. 16 hem. )

Consequence

RTL4
NM_001395362.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.121

Variant links:

Genes affected

RTL4 (HGNC:25214): (retrotransposon Gag like 4) Predicted to enable nucleic acid binding activity and zinc ion binding activity. Predicted to act upstream of or within cognition and norepinephrine metabolic process. [provided by Alliance of Genome Resources, Apr 2022]

RTL4 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=0.018396407).

BS2

High Hemizygotes in GnomAdExome at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTL4	NM_001395362.2 linkuse as main transcript	c.548A>C	p.Gln183Pro	missense_variant	5/5	ENST00000695839.1
RTL4	NM_001004308.3 linkuse as main transcript	c.548A>C	p.Gln183Pro	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
RTL4	ENST00000695839.1 linkuse as main transcript	c.548A>C	p.Gln183Pro	missense_variant	5/5	NM_001395362.2	P1
RTL4	ENST00000340433.4 linkuse as main transcript	c.548A>C	p.Gln183Pro	missense_variant	4/4		P1
RTL4	ENST00000695808.1 linkuse as main transcript	c.548A>C	p.Gln183Pro	missense_variant	3/3		P1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111677

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33837

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:

0.000563

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:

0.000148

AC:

AN:

181965

Hom.:

AF XY:

0.000150

AC XY:

AN XY:

66815

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00195

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:

0.0000410

AC:

AN:

1097894

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

363278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00146

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111677

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33837

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000563

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000422

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000222

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 21, 2024

The c.548A>C (p.Q183P) alteration is located in exon 3 (coding exon 1) of the ZCCHC16 gene. This alteration results from a A to C substitution at nucleotide position 548, causing the glutamine (Q) at amino acid position 183 to be replaced by a proline (P). 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

0.084

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.64

Cadd

Benign

1.1

Dann

Benign

0.84

DEOGEN2

Benign

0.20

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.32

M_CAP

Benign

0.0047

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-3.8

REVEL

Benign

0.020

Sift

Uncertain

0.014

Sift4G

Benign

0.19

Polyphen

0.0010

Vest4

0.20

MutPred

0.36

Gain of glycosylation at Q183 (P = 0.0651);

MVP

0.32

MPC

0.014

ClinPred

0.045

GERP RS

0.040

Varity_R

0.58

gMVP

0.86

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