chrX-9739492-C-G
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_000273.3(GPR143):āc.1113G>Cā(p.Leu371=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000647 in 1,082,753 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: not found (cov: 24)
Exomes š: 0.0000065 ( 0 hom. 4 hem. )
Consequence
GPR143
NM_000273.3 synonymous
NM_000273.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.441
Genes affected
GPR143 (HGNC:20145): (G protein-coupled receptor 143) This gene encodes a protein that binds to heterotrimeric G proteins and is targeted to melanosomes in pigment cells. This protein is thought to be involved in intracellular signal transduction mechanisms. Mutations in this gene cause ocular albinism type 1, also referred to as Nettleship-Falls type ocular albinism, a severe visual disorder. A related pseudogene has been identified on chromosome Y. [provided by RefSeq, Dec 2009]
TBL1X (HGNC:11585): (transducin beta like 1 X-linked) The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This encoded protein is found as a subunit in corepressor SMRT (silencing mediator for retinoid and thyroid receptors) complex along with histone deacetylase 3 protein. This gene is located adjacent to the ocular albinism gene and it is thought to be involved in the pathogenesis of the ocular albinism with late-onset sensorineural deafness phenotype. Four transcript variants encoding two different isoforms have been found for this gene. This gene is highly similar to the Y chromosome TBL1Y gene. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant X-9739492-C-G is Benign according to our data. Variant chrX-9739492-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1545823.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.441 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GPR143 | NM_000273.3 | c.1113G>C | p.Leu371= | synonymous_variant | 8/9 | ENST00000467482.6 | |
LOC105373126 | XR_950507.2 | n.1620+773C>G | intron_variant, non_coding_transcript_variant | ||||
GPR143 | XM_005274541.4 | c.1113G>C | p.Leu371= | synonymous_variant | 8/9 | ||
GPR143 | XM_024452388.2 | c.861G>C | p.Leu287= | synonymous_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GPR143 | ENST00000467482.6 | c.1113G>C | p.Leu371= | synonymous_variant | 8/9 | 1 | NM_000273.3 | P1 | |
TBL1X | ENST00000647060.1 | c.1555-1290C>G | intron_variant | ||||||
GPR143 | ENST00000487206.1 | n.228G>C | non_coding_transcript_exon_variant | 1/2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000567 AC: 1AN: 176464Hom.: 0 AF XY: 0.0000163 AC XY: 1AN XY: 61396
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GnomAD4 exome AF: 0.00000646 AC: 7AN: 1082753Hom.: 0 Cov.: 29 AF XY: 0.0000114 AC XY: 4AN XY: 349421
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GnomAD4 genome Cov.: 24
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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 | Jul 27, 2022 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at