chr3-186666156-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000412.5(HRG):c.125G>A(p.Arg42Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,614,178 control chromosomes in the GnomAD database, including 19 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. R42L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000412.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HRG | NM_000412.5 | c.125G>A | p.Arg42Gln | missense_variant | 1/7 | ENST00000232003.5 | |
HRG-AS1 | XR_924801.3 | n.291-14285C>T | intron_variant, non_coding_transcript_variant | ||||
HRG | XM_005247415.5 | c.125G>A | p.Arg42Gln | missense_variant | 1/7 | ||
HRG-AS1 | XR_001741059.2 | n.291-14285C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HRG | ENST00000232003.5 | c.125G>A | p.Arg42Gln | missense_variant | 1/7 | 1 | NM_000412.5 | P1 | |
HRG-AS1 | ENST00000630178.2 | n.238+52311C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00313 AC: 476AN: 152208Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00259 AC: 651AN: 251374Hom.: 1 AF XY: 0.00251 AC XY: 341AN XY: 135862
GnomAD4 exome AF: 0.00381 AC: 5567AN: 1461852Hom.: 16 Cov.: 31 AF XY: 0.00367 AC XY: 2667AN XY: 727230
GnomAD4 genome ? AF: 0.00312 AC: 476AN: 152326Hom.: 3 Cov.: 32 AF XY: 0.00309 AC XY: 230AN XY: 74480
ClinVar
Submissions by phenotype
Hereditary thrombophilia due to congenital histidine-rich (poly-L) glycoprotein deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology | - | - - |
Thrombus Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | HRG: BP4, BS2 - |
HRG-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 09, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at