chr10-76036082-T-G

Position:

• chr10-76036082-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001305581.2(LRMDA):​c.206T>G​(p.Leu69Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LRMDA NM_001305581.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.41

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33262482).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRMDA	NM_001305581.2	c.206T>G	p.Leu69Arg	missense_variant	3/7	ENST00000611255.5	NP_001292510.1
LRMDA	NM_032024.5	c.122T>G	p.Leu41Arg	missense_variant	2/6		NP_114413.1
LRMDA	NR_131178.2	n.560T>G		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRMDA	ENST00000611255.5	c.206T>G	p.Leu69Arg	missense_variant	3/7	5	NM_001305581.2	ENSP00000480240	P1
LRMDA	ENST00000372499.5	c.122T>G	p.Leu41Arg	missense_variant	2/6	1		ENSP00000361577
LRMDA	ENST00000593699.5	n.560T>G		non_coding_transcript_exon_variant	4/8	1
LRMDA	ENST00000593817.1	n.167T>G		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 12, 2022

This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 41 of the C10orf11 protein (p.Leu41Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with C10orf11-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	.;T;T
Eigen	Benign	-0.064
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PROVEAN	Uncertain	-3.0	.;D;.
REVEL	Benign	0.25
Sift	Benign	0.41	.;T;.
Sift4G	Benign	0.44	T;T;T
Polyphen		0.099	.;B;.
Vest4		0.78
MutPred		0.26		.;Gain of disorder (P = 0.0308);.;
MVP		0.54
MPC		0.22
ClinPred		0.70	D
GERP RS		4.4
Varity_R		0.64
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-77795840;