chr9-127818173-C-T
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM5BP4_StrongBP6BS1BS2
The NM_001114753.3(ENG):c.1633G>A(p.Gly545Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000637 in 1,614,188 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G545D) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001114753.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ENG | NM_001114753.3 | c.1633G>A | p.Gly545Ser | missense_variant | 12/15 | ENST00000373203.9 | |
LOC102723566 | NR_136302.1 | n.1378-138C>T | intron_variant, non_coding_transcript_variant | ||||
ENG | NM_000118.4 | c.1633G>A | p.Gly545Ser | missense_variant | 12/14 | ||
ENG | NM_001278138.2 | c.1087G>A | p.Gly363Ser | missense_variant | 12/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENG | ENST00000373203.9 | c.1633G>A | p.Gly545Ser | missense_variant | 12/15 | 1 | NM_001114753.3 | P2 | |
ENST00000439298.5 | n.1378-138C>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000361 AC: 55AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000521 AC: 131AN: 251296Hom.: 0 AF XY: 0.000456 AC XY: 62AN XY: 135870
GnomAD4 exome AF: 0.000666 AC: 973AN: 1461876Hom.: 2 Cov.: 31 AF XY: 0.000660 AC XY: 480AN XY: 727242
GnomAD4 genome AF: 0.000361 AC: 55AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74476
ClinVar
Submissions by phenotype
Telangiectasia, hereditary hemorrhagic, type 1 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | May 04, 2023 | European Non-Finnish population allele frequency is 0.12% (rs142896669, 54/35,428 alleles, 0 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.4.1, this variant is classified as LIKELY BENIGN. Following criteria are met: BS1 - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Pulmonary hypertension, primary, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | Rare Disease Genomics Group, St George's University of London | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 25, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 2 probands, no segs in HGMD; ExAC: 0.2% (25/11560) Latino chromosomes - |
Pulmonary arterial hypertension associated with congenital heart disease Uncertain:1
Uncertain significance, criteria provided, single submitter | case-control | Wendy Chung Laboratory, Columbia University Medical Center | Jun 27, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2020 | See Variant Classification Assertion Criteria. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Hereditary hemorrhagic telangiectasia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at