Variant X-135052101-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001078172.2(RTL8A):c.8G>A(p.Gly3Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,198,412 control chromosomes in the GnomAD database, including 4 homozygotes. There are 558 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 0.0010 ( 1 hom., 33 hem., cov: 26)

Exomes 𝑓: 0.0016 ( 3 hom. 525 hem. )

Consequence

RTL8A
NM_001078172.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184

Variant links:

Genes affected

RTL8A (HGNC:24514): (retrotransposon Gag like 8A) Predicted to be active in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

RTL8A 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=0.008345306).

BS2

High Hemizygotes in GnomAd4 at 33 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL8A	NM_001078172.2 linkuse as main transcript	c.8G>A	p.Gly3Asp	missense_variant	1/1	ENST00000370775.3	NP_001071640.1
RTL8A	NM_001134321.2 linkuse as main transcript	c.8G>A	p.Gly3Asp	missense_variant	1/2		NP_001127793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RTL8A	ENST00000370775.3 linkuse as main transcript	c.8G>A	p.Gly3Asp	missense_variant	1/1		NM_001078172.2	ENSP00000375267	P1
RTL8A	ENST00000522309.1 linkuse as main transcript	n.41G>A		non_coding_transcript_exon_variant	1/2	1
RTL8A	ENST00000520964.1 linkuse as main transcript	n.96G>A		non_coding_transcript_exon_variant	1/2	3
RTL8A	ENST00000518153.1 linkuse as main transcript			upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000995

AC:

113

AN:

113516

Hom.:

Cov.:

AF XY:

0.000926

AC XY:

AN XY:

35644

show subpopulations

Gnomad AFR

AF:

0.0000638

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000549

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00178

Gnomad OTH

AF:

0.000648

GnomAD3 exomes

AF:

0.000812

AC:

133

AN:

163793

Hom.:

AF XY:

0.000878

AC XY:

AN XY:

53511

show subpopulations

Gnomad AFR exome

AF:

0.000170

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000866

Gnomad NFE exome

AF:

0.00152

Gnomad OTH exome

AF:

0.000755

GnomAD4 exome

AF:

0.00157

AC:

1706

AN:

1084845

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

525

AN XY:

353089

show subpopulations

Gnomad4 AFR exome

AF:

0.000385

Gnomad4 AMR exome

AF:

0.000267

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000927

Gnomad4 NFE exome

AF:

0.00189

Gnomad4 OTH exome

AF:

0.00156

GnomAD4 genome

AF:

0.000995

AC:

113

AN:

113567

Hom.:

Cov.:

AF XY:

0.000924

AC XY:

AN XY:

35705

show subpopulations

Gnomad4 AFR

AF:

0.0000637

Gnomad4 AMR

AF:

0.000548

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00141

Gnomad4 NFE

AF:

0.00178

Gnomad4 OTH

AF:

0.000641

Alfa

AF:

0.00121

Hom.:

Bravo

AF:

0.000850

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00173

AC:

ESP6500AA

AF:

0.000304

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000732

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

Oct 13, 2021

The c.8G>A (p.G3D) alteration is located in exon 1 (coding exon 1) of the FAM127B gene. This alteration results from a G to A substitution at nucleotide position 8, causing the glycine (G) at amino acid position 3 to be replaced by an aspartic acid (D). 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

0.13

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0068

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.59

M_CAP

Benign

0.0032

MetaRNN

Benign

0.0083

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.2

REVEL

Benign

0.060

Sift

Benign

0.52

Sift4G

Benign

0.35

Polyphen

0.0020

Vest4

0.12

MVP

0.15

MPC

0.79

ClinPred

0.012

GERP RS

0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.17

gMVP

0.70

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