Variant X-135032567-G-A 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_001078171.2(RTL8C):c.184G>A(p.Ala62Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,097,325 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. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

RTL8C
NM_001078171.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.467

Variant links:

Genes affected

RTL8C (HGNC:2569): (retrotransposon Gag like 8C) Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

RTL8C links:

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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=0.051636696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL8C	NM_001078171.2 linkuse as main transcript	c.184G>A	p.Ala62Thr	missense_variant	1/1	ENST00000257013.9	NP_001071639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RTL8C	ENST00000257013.9 linkuse as main transcript	c.184G>A	p.Ala62Thr	missense_variant	1/1		NM_001078171.2	ENSP00000257013	P1
RTL8C	ENST00000464369.1 linkuse as main transcript	n.186G>A		non_coding_transcript_exon_variant	1/2	5
RTL8C	ENST00000495563.5 linkuse as main transcript	n.186G>A		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000553

AC:

AN:

180916

Hom.:

AF XY:

0.0000150

AC XY:

AN XY:

66756

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000739

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:

0.00000182

AC:

AN:

1097325

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

362899

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:

0.00

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

Cov.:

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.00000378

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

May 23, 2023

The c.184G>A (p.A62T) alteration is located in exon 1 (coding exon 1) of the FAM127A gene. This alteration results from a G to A substitution at nucleotide position 184, causing the alanine (A) at amino acid position 62 to be replaced by a threonine (T). 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

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0072

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.71

M_CAP

Benign

0.010

MetaRNN

Benign

0.052

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.0

REVEL

Benign

0.039

Sift

Benign

0.36

Sift4G

Uncertain

0.060

Polyphen

0.0030

Vest4

0.059

MutPred

0.36

Loss of ubiquitination at K64 (P = 0.0618);

MVP

0.15

MPC

1.3

ClinPred

0.066

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.83

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