7-155806384-G-A
Variant summary
Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7
The NM_000193.4(SHH):c.474C>T(p.Tyr158Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,613,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_000193.4 synonymous
Scores
Clinical Significance
Conservation
Publications
- holoprosencephaly 3Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- microphthalmia, isolated, with coloboma 5Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia
- polydactyly of a triphalangeal thumbInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
- solitary median maxillary central incisor syndromeInheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: G2P, Ambry Genetics
- skeletal system disorderInheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- autosomal dominant preaxial polydactyly-upperback hypertrichosis syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hypoplastic tibiae-postaxial polydactyly syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- microphthalmia, isolated, with colobomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- syndactyly type 4Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- triphalangeal thumb-polysyndactyly syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- holoprosencephalyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 34 show subpopulations
GnomAD2 exomes AF: 0.0000120 AC: 3AN: 250972 AF XY: 0.0000147 show subpopulations
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461354Hom.: 0 Cov.: 34 AF XY: 0.0000330 AC XY: 24AN XY: 727010 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74384 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
Inborn genetic diseases Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at