10-75783007-A-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The ENST00000372499.5(LRMDA):c.32A>C(p.His11Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,614,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

LRMDA
ENST00000372499.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.40

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009788305).

BP6

Variant 10-75783007-A-C is Benign according to our data. Variant chr10-75783007-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1681424.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-75783007-A-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000788 (12/152322) while in subpopulation EAS AF= 0.00232 (12/5176). AF 95% confidence interval is 0.00134. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRMDA	NM_001305581.2 linkuse as main transcript	c.132-253001A>C		intron_variant		ENST00000611255.5
LRMDA	NM_032024.5 linkuse as main transcript	c.32A>C	p.His11Pro	missense_variant	1/6
LRMDA	NR_131178.2 linkuse as main transcript	n.86-99649A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LRMDA	ENST00000372499.5 linkuse as main transcript	c.32A>C	p.His11Pro	missense_variant	1/6	1
LRMDA	ENST00000611255.5 linkuse as main transcript	c.132-253001A>C		intron_variant		5	NM_001305581.2	P1
LRMDA	ENST00000593699.5 linkuse as main transcript	n.86-99649A>C		intron_variant, non_coding_transcript_variant		1
LRMDA	ENST00000593817.1 linkuse as main transcript	n.92+181676A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000347

AC:

AN:

250932

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00468

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1461840

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00169

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00232

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000117

ExAC

AF:

0.000296

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 19, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Benign

0.87

DEOGEN2

Benign

0.0011

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.31

M_CAP

Benign

0.0076

MetaRNN

Benign

0.0098

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N

PROVEAN

Benign

-0.33

REVEL

Benign

0.18

Sift

Benign

0.29

Sift4G

Benign

0.26

Polyphen

0.0010

Vest4

0.41

MutPred

0.24

Gain of glycosylation at H11 (P = 0.0202);

MVP

0.66

MPC

0.19

ClinPred

0.082

GERP RS

4.5

Varity_R

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