Variant 10-76324426-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001305581.2(LRMDA):c.542C>T(p.Ser181Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0201 in 1,614,016 control chromosomes in the GnomAD database, including 778 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 224 hom., cov: 32)

Exomes 𝑓: 0.018 ( 554 hom. )

Consequence

LRMDA
NM_001305581.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.27

Variant links:

Genes affected

LRMDA (HGNC:23405): (leucine rich melanocyte differentiation associated) This gene encodes a leucine-rich repeat protein. The encoded protein is thought to play a role in melanocyte differentiation. Mutations in this gene have been associated with autosomal recessive oculocutaneous albinism 7 (OCA7). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

LRMDA links:

LRMDA (HGNC:):

LRMDA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025200844).

BP6

Variant 10-76324426-C-T is Benign according to our data. Variant chr10-76324426-C-T is described in ClinVar as [Benign]. Clinvar id is 261991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2 linkuse as main transcript	c.542C>T	p.Ser181Phe	missense_variant	6/7	ENST00000611255.5	NP_001292510.1	A0A087WWI0
LRMDA	NM_032024.5 linkuse as main transcript	c.458C>T	p.Ser153Phe	missense_variant	5/6		NP_114413.1	Q9H2I8
LRMDA	NR_131178.2 linkuse as main transcript	n.896C>T		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5 linkuse as main transcript	c.542C>T	p.Ser181Phe	missense_variant	6/7	5	NM_001305581.2	ENSP00000480240.1		A0A087WWI0

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6056

AN:

152038

Hom.:

223

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0987

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0197

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.0751

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0149

Gnomad OTH

AF:

0.0354

GnomAD3 exomes

AF:

0.0260

AC:

6545

AN:

251444

Hom.:

207

AF XY:

0.0264

AC XY:

3582

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.00714

Gnomad EAS exome

AF:

0.0369

Gnomad SAS exome

AF:

0.0667

Gnomad FIN exome

AF:

0.00494

Gnomad NFE exome

AF:

0.0132

Gnomad OTH exome

AF:

0.0202

GnomAD4 exome

AF:

0.0180

AC:

26340

AN:

1461860

Hom.:

554

Cov.:

AF XY:

0.0191

AC XY:

13887

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0986

Gnomad4 AMR exome

AF:

0.0114

Gnomad4 ASJ exome

AF:

0.00612

Gnomad4 EAS exome

AF:

0.0225

Gnomad4 SAS exome

AF:

0.0630

Gnomad4 FIN exome

AF:

0.00520

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.0239

GnomAD4 genome

AF:

0.0399

AC:

6072

AN:

152156

Hom.:

224

Cov.:

AF XY:

0.0387

AC XY:

2880

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0987

Gnomad4 AMR

AF:

0.0196

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.0265

Gnomad4 SAS

AF:

0.0752

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.0149

Gnomad4 OTH

AF:

0.0384

Alfa

AF:

0.0171

Hom.:

Bravo

AF:

0.0416

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.0906

AC:

399

ESP6500EA

AF:

0.0143

AC:

123

ExAC

AF:

0.0283

AC:

3436

Asia WGS

AF:

0.0830

AC:

286

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0143

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0072

.;T;.

Eigen

Benign

0.085

Eigen_PC

Benign

0.00052

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-1.2

PROVEAN

Benign

-2.2

.;N;.

REVEL

Benign

0.10

Sift

Uncertain

0.011

.;D;.

Sift4G

Uncertain

0.028

D;D;D

Polyphen

0.90

.;P;.

Vest4

0.14

MPC

0.15

ClinPred

0.045

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.30

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