Variant 7-150337409-T-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_001142928.2(LRRC61):c.548T>C(p.Leu183Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

LRRC61
NM_001142928.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

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:

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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=0.10516137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRC61	NM_001142928.2 linkuse as main transcript	c.548T>C	p.Leu183Ser	missense_variant	3/3	ENST00000359623.9	NP_001136400.1
LRRC61	NM_001363433.1 linkuse as main transcript	c.548T>C	p.Leu183Ser	missense_variant	3/3		NP_001350362.1
LRRC61	NM_001363434.1 linkuse as main transcript	c.548T>C	p.Leu183Ser	missense_variant	3/3		NP_001350363.1
LRRC61	NM_023942.3 linkuse as main transcript	c.548T>C	p.Leu183Ser	missense_variant	2/2		NP_076431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRRC61	ENST00000359623.9 linkuse as main transcript	c.548T>C	p.Leu183Ser	missense_variant	3/3	2	NM_001142928.2	ENSP00000352642	P1
LRRC61	ENST00000323078.7 linkuse as main transcript	c.548T>C	p.Leu183Ser	missense_variant	2/2	1		ENSP00000339047	P1
LRRC61	ENST00000493307.1 linkuse as main transcript	c.548T>C	p.Leu183Ser	missense_variant	4/4	5		ENSP00000420560	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1453396

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

723454

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Dec 27, 2022

The c.548T>C (p.L183S) alteration is located in exon 3 (coding exon 1) of the LRRC61 gene. This alteration results from a T to C substitution at nucleotide position 548, causing the leucine (L) at amino acid position 183 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

Benign

0.18

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.041

T;T;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.38

.;.;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.022

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.067

B;B;B

Vest4

0.18

MutPred

0.40

Gain of phosphorylation at L183 (P = 0.0068);Gain of phosphorylation at L183 (P = 0.0068);Gain of phosphorylation at L183 (P = 0.0068);

MVP

0.37

MPC

0.28

ClinPred

0.72

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.18

gMVP

0.55

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