Variant 2-14634592-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145175.4(LRATD1):c.613G>C(p.Glu205Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000705 in 1,502,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000072 ( 0 hom. )

Consequence

LRATD1
NM_145175.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

LRATD1 (HGNC:20743): (LRAT domain containing 1) Involved in cell morphogenesis and cell motility. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRATD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14025953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRATD1	NM_145175.4 linkuse as main transcript	c.613G>C	p.Glu205Gln	missense_variant	2/2	ENST00000295092.3	NP_660158.2
LRATD1	NM_001369364.1 linkuse as main transcript	c.613G>C	p.Glu205Gln	missense_variant	3/3		NP_001356293.1
LRATD1	NR_144632.2 linkuse as main transcript	n.870G>C		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRATD1	ENST00000295092.3 linkuse as main transcript	c.613G>C	p.Glu205Gln	missense_variant	2/2	1	NM_145175.4	ENSP00000295092	P1	Q96KN4-1
LRATD1	ENST00000331243.4 linkuse as main transcript	c.613G>C	p.Glu205Gln	missense_variant	3/3	3		ENSP00000330681	P1	Q96KN4-1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000376

AC:

AN:

133038

Hom.:

AF XY:

0.0000285

AC XY:

AN XY:

70112

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000860

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000718

AC:

AN:

1350702

Hom.:

Cov.:

AF XY:

0.0000652

AC XY:

AN XY:

659912

show subpopulations

Gnomad4 AFR exome

AF:

0.0000333

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000901

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000118

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000680

ExAC

AF:

0.00000836

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

Jun 01, 2023

The c.613G>C (p.E205Q) alteration is located in exon 2 (coding exon 1) of the FAM84A gene. This alteration results from a G to C substitution at nucleotide position 613, causing the glutamic acid (E) at amino acid position 205 to be replaced by a glutamine (Q). 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

0.095

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;T

Eigen

Benign

0.019

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.89

.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

0.18

N;N

REVEL

Benign

0.047

Sift

Benign

0.27

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.52

P;P

Vest4

0.25

MutPred

0.22

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

MVP

0.52

MPC

0.67

ClinPred

0.42

GERP RS

4.2

Varity_R

0.15

gMVP

0.52

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