10-76036082-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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

Scores

1
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41
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]

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ACMG classification

Classification made for transcript

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
LRMDANM_001305581.2 linkuse as main transcriptc.206T>G p.Leu69Arg missense_variant 3/7 ENST00000611255.5 NP_001292510.1
LRMDANM_032024.5 linkuse as main transcriptc.122T>G p.Leu41Arg missense_variant 2/6 NP_114413.1
LRMDANR_131178.2 linkuse as main transcriptn.560T>G non_coding_transcript_exon_variant 4/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRMDAENST00000611255.5 linkuse as main transcriptc.206T>G p.Leu69Arg missense_variant 3/75 NM_001305581.2 ENSP00000480240 P1
LRMDAENST00000372499.5 linkuse as main transcriptc.122T>G p.Leu41Arg missense_variant 2/61 ENSP00000361577
LRMDAENST00000593699.5 linkuse as main transcriptn.560T>G non_coding_transcript_exon_variant 4/81
LRMDAENST00000593817.1 linkuse as main transcriptn.167T>G non_coding_transcript_exon_variant 2/23

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
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 12, 2022This 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; API