Variant 8-126556903-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_174911.5(LRATD2):c.487C>A(p.Arg163Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRATD2
NM_174911.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

LRATD2 (HGNC:24166): (LRAT domain containing 2) Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRATD2 links:

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

PCAT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRATD2	NM_174911.5 link	c.487C>A	p.Arg163Ser	missense_variant	2/2	ENST00000304916.4	NP_777571.1	Q96KN1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRATD2	ENST00000304916.4 link	c.487C>A	p.Arg163Ser	missense_variant	2/2	1	NM_174911.5	ENSP00000302578.3	Q96KN1
LRATD2	ENST00000652209.1 link	c.487C>A	p.Arg163Ser	missense_variant	1/1			ENSP00000498944.1	Q96KN1
PCAT1	ENST00000524320.2 link	n.581G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456734

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724956

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:

0.00

GnomAD4 genome

Cov.:

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

Jun 28, 2022

The c.487C>A (p.R163S) alteration is located in exon 2 (coding exon 1) of the FAM84B gene. This alteration results from a C to A substitution at nucleotide position 487, causing the arginine (R) at amino acid position 163 to be replaced by a serine (S). 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

Pathogenic

0.79

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.019

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.63

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

REVEL

Benign

0.23

Sift

Benign

0.56

Sift4G

Benign

0.47

Polyphen

1.0

Vest4

0.72

MutPred

0.36

Loss of sheet (P = 0.0457);

MVP

0.59

MPC

1.7

ClinPred

0.43

GERP RS

1.7

Varity_R

0.16

gMVP

0.82

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over