Variant X-135052089-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001078172.2(RTL8A):c.20T>C(p.Leu7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,205,540 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000088 ( 0 hom., 1 hem., cov: 26)

Exomes 𝑓: 0.0000037 ( 0 hom. 3 hem. )

Consequence

RTL8A
NM_001078172.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2907338).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL8A	NM_001078172.2 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	1/1	ENST00000370775.3	NP_001071640.1
RTL8A	NM_001134321.2 linkuse as main transcript	c.20T>C	p.Leu7Pro	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.20T>C	p.Leu7Pro	missense_variant	1/1		NM_001078172.2	ENSP00000375267	P1
RTL8A	ENST00000522309.1 linkuse as main transcript	n.53T>C		non_coding_transcript_exon_variant	1/2	1
RTL8A	ENST00000518153.1 linkuse as main transcript	n.2T>C		non_coding_transcript_exon_variant	1/2	2
RTL8A	ENST00000520964.1 linkuse as main transcript	n.108T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00000883

AC:

AN:

113309

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

35467

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

GnomAD4 exome

AF:

0.00000366

AC:

AN:

1092231

Hom.:

Cov.:

AF XY:

0.00000837

AC XY:

AN XY:

358571

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:

0.00000477

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000883

AC:

AN:

113309

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

35467

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:

0.0000113

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

Mar 04, 2024

The c.20T>C (p.L7P) alteration is located in exon 1 (coding exon 1) of the FAM127B gene. This alteration results from a T to C substitution at nucleotide position 20, causing the leucine (L) at amino acid position 7 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.096

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.65

M_CAP

Benign

0.0080

MetaRNN

Benign

0.29

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.24

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.018

Polyphen

0.99

Vest4

0.34

MutPred

0.65

Loss of helix (P = 0.0033);

MVP

0.16

MPC

1.9

ClinPred

0.60

GERP RS

1.1

Varity_R

0.44

gMVP

0.90

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