chr10-101775156-G-A
Variant summary
Our verdict is Likely benign. The variant received -6 ACMG points: 3P and 9B. PM1PP2BP4_StrongBP6BS1
The NM_033163.5(FGF8):c.130C>T(p.Arg44Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000976 in 1,547,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. R44P) has been classified as Uncertain significance.
Frequency
Consequence
NM_033163.5 missense
Scores
Clinical Significance
Conservation
Publications
- hypogonadotropic hypogonadism 6 with or without anosmiaInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
- hypogonadotropic hypogonadismInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Kallmann syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- holoprosencephalyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Likely_benign. The variant received -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152168Hom.: 0 Cov.: 31 show subpopulations
GnomAD2 exomes AF: 0.000140 AC: 21AN: 149474 AF XY: 0.000149 show subpopulations
GnomAD4 exome AF: 0.000102 AC: 142AN: 1395728Hom.: 0 Cov.: 32 AF XY: 0.000129 AC XY: 89AN XY: 688446 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152168Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6AN XY: 74338 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Peters plus syndrome Uncertain:1
- -
Holoprosencephaly sequence Benign:1
Compatible clinical findings, but predicted to be benign on the basis of experimental data and ACMG criteria:BS3/BS1;BP4. Six unrelated detections in ExAC exceeds the birth incidence of Holopresencephaly (1:10,1000 to 1:20,000). -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at