Variant X-135051924-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001078172.2(RTL8A):c.185C>G(p.Ala62Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000033 in 1,210,961 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 0.0000088 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

RTL8A
NM_001078172.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.273

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:

RTL8A (HGNC:):

RTL8A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043509483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL8A	NM_001078172.2 linkuse as main transcript	c.185C>G	p.Ala62Gly	missense_variant	1/1	ENST00000370775.3	NP_001071640.1	Q9BWD3
RTL8A	NM_001134321.2 linkuse as main transcript	c.185C>G	p.Ala62Gly	missense_variant	1/2		NP_001127793.1	Q9BWD3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RTL8A	ENST00000370775.3 linkuse as main transcript	c.185C>G	p.Ala62Gly	missense_variant	1/1	6	NM_001078172.2	ENSP00000375267.1	Q9BWD3
RTL8A	ENST00000522309.1 linkuse as main transcript	n.218C>G		non_coding_transcript_exon_variant	1/2	1
RTL8A	ENST00000518153.1 linkuse as main transcript	n.167C>G		non_coding_transcript_exon_variant	1/2	2
RTL8A	ENST00000520964.1 linkuse as main transcript	n.273C>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00000884

AC:

AN:

113083

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35211

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:

0.000361

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

181053

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

66901

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:

0.000158

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000273

AC:

AN:

1097826

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363226

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:

0.0000554

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000884

AC:

AN:

113135

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35273

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:

0.000362

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000247

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

Aug 02, 2022

The c.185C>G (p.A62G) alteration is located in exon 1 (coding exon 1) of the FAM127B gene. This alteration results from a C to G substitution at nucleotide position 185, causing the alanine (A) at amino acid position 62 to be replaced by a glycine (G). 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

0.16

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

FATHMM_MKL

Benign

0.11

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0087

MetaRNN

Benign

0.044

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.3

REVEL

Benign

0.044

Sift

Benign

0.12

Sift4G

Benign

0.066

Polyphen

0.18

Vest4

0.037

MutPred

0.46

Loss of stability (P = 0.0255);

MVP

0.16

MPC

0.74

ClinPred

0.13

GERP RS

1.4

Varity_R

0.23

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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