rs75852090

chr10-76557218-G-Achr10-76557218-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001305581.2(LRMDA):c.611G>A(p.Gly204Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00509 in 1,613,916 control chromosomes in the GnomAD database, including 366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G204G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.028 (195 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (171 hom.)
• Consequence: LRMDA NM_001305581.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.57

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043112934).
• BP6: Variant 10-76557218-G-A is Benign according to our data. Variant chr10-76557218-G-A is described in ClinVar as [Benign]. Clinvar id is 261992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRMDA	NM_001305581.2	c.611G>A	p.Gly204Glu	missense_variant	7/7	ENST00000611255.5
LRMDA	NM_032024.5	c.527G>A	p.Gly176Glu	missense_variant	6/6
LRMDA	NR_131178.2	n.965G>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRMDA	ENST00000611255.5	c.611G>A	p.Gly204Glu	missense_variant	7/7	5	NM_001305581.2	P1

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4266 AN: 152064 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.0960

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.00717 AC: 1804 AN: 251456 Hom.: 80 AF XY: 0.00510 AC XY: 693 AN XY: 135898

Gnomad AFR exome AF: 0.0991

Gnomad AMR exome AF: 0.00414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00270 AC: 3942 AN: 1461734 Hom.: 171 Cov.: 30 AF XY: 0.00223 AC XY: 1619 AN XY: 727190

Gnomad4 AFR exome AF: 0.0958

Gnomad4 AMR exome AF: 0.00470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000117

Gnomad4 OTH exome AF: 0.00576

GnomAD4 genome AF: 0.0281 AC: 4270 AN: 152182 Hom.: 195 Cov.: 32 AF XY: 0.0267 AC XY: 1987 AN XY: 74406

Gnomad4 AFR AF: 0.0958

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00509 Hom.: 66

Bravo AF: 0.0319

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0910 AC: 401

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00906 AC: 1100

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.32
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D;D;D
MetaRNN	Benign	0.0043	T;T;T
MetaSVM	Benign	-0.76	T
MutationTaster	Benign	1.0	D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	.;D;.
Vest4		0.54
MVP		0.90
MPC		0.64
ClinPred		0.029	T
GERP RS		6.0
Varity_R		0.77
gMVP		0.64

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

Other links and lift over

dbSNP: rs75852090; hg19: chr10-78316976;