10-76036069-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_001305581.2(LRMDA):c.193C>T(p.Leu65=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00337 in 1,614,052 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0021 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0035 ( 16 hom. )
Consequence
LRMDA
NM_001305581.2 synonymous
NM_001305581.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.61
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 Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 10-76036069-C-T is Benign according to our data. Variant chr10-76036069-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 261986.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=1, Uncertain_significance=1}. Variant chr10-76036069-C-T is described in Lovd as [Benign]. Variant chr10-76036069-C-T is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00206 (313/152174) while in subpopulation NFE AF= 0.00404 (275/68044). AF 95% confidence interval is 0.00365. There are 0 homozygotes in gnomad4. There are 128 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRMDA | NM_001305581.2 | c.193C>T | p.Leu65= | synonymous_variant | 3/7 | ENST00000611255.5 | |
LRMDA | NM_032024.5 | c.109C>T | p.Leu37= | synonymous_variant | 2/6 | ||
LRMDA | NR_131178.2 | n.547C>T | non_coding_transcript_exon_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRMDA | ENST00000611255.5 | c.193C>T | p.Leu65= | synonymous_variant | 3/7 | 5 | NM_001305581.2 | P1 | |
LRMDA | ENST00000372499.5 | c.109C>T | p.Leu37= | synonymous_variant | 2/6 | 1 | |||
LRMDA | ENST00000593699.5 | n.547C>T | non_coding_transcript_exon_variant | 4/8 | 1 | ||||
LRMDA | ENST00000593817.1 | n.154C>T | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00206 AC: 313AN: 152174Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00190 AC: 477AN: 251450Hom.: 1 AF XY: 0.00183 AC XY: 248AN XY: 135888
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GnomAD4 exome AF: 0.00351 AC: 5134AN: 1461878Hom.: 16 Cov.: 32 AF XY: 0.00342 AC XY: 2485AN XY: 727238
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | LRMDA: BP4, BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 30, 2018 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Oculocutaneous albinism type 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Jun 28, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at