Variant 7-150337303-G-A 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_001142928.2(LRRC61):c.442G>A(p.Ala148Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,451,290 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LRRC61
NM_001142928.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.02

Variant links:

Genes affected

LRRC61 (HGNC:21704): (leucine rich repeat containing 61) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

LRRC61 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=0.069842726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRRC61	NM_001142928.2 linkuse as main transcript	c.442G>A	p.Ala148Thr	missense_variant	3/3	ENST00000359623.9
LRRC61	NM_001363433.1 linkuse as main transcript	c.442G>A	p.Ala148Thr	missense_variant	3/3
LRRC61	NM_001363434.1 linkuse as main transcript	c.442G>A	p.Ala148Thr	missense_variant	3/3
LRRC61	NM_023942.3 linkuse as main transcript	c.442G>A	p.Ala148Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRRC61	ENST00000359623.9 linkuse as main transcript	c.442G>A	p.Ala148Thr	missense_variant	3/3	2	NM_001142928.2	P1
LRRC61	ENST00000323078.7 linkuse as main transcript	c.442G>A	p.Ala148Thr	missense_variant	2/2	1		P1
LRRC61	ENST00000493307.1 linkuse as main transcript	c.442G>A	p.Ala148Thr	missense_variant	4/4	5		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000822

AC:

AN:

243362

Hom.:

AF XY:

0.00000756

AC XY:

AN XY:

132280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1451290

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

722472

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jan 10, 2023

The c.442G>A (p.A148T) alteration is located in exon 3 (coding exon 1) of the LRRC61 gene. This alteration results from a G to A substitution at nucleotide position 442, causing the alanine (A) at amino acid position 148 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

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.0029

T;T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.44

M_CAP

Benign

0.0031

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;L

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.80

N;N;N

REVEL

Benign

0.045

Sift

Benign

0.26

T;T;T

Sift4G

Benign

0.40

T;T;T

Polyphen

0.0030

B;B;B

Vest4

0.088

MutPred

0.46

Loss of catalytic residue at A148 (P = 0.1072);Loss of catalytic residue at A148 (P = 0.1072);Loss of catalytic residue at A148 (P = 0.1072);

MVP

0.085

MPC

0.18

ClinPred

0.038

GERP RS

0.90

Varity_R

0.044

gMVP

0.19

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