14-102027708-G-T
Variant summary
Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001376.5(DYNC1H1):c.9138G>T(p.Ser3046Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000446 in 1,614,140 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S3046S) has been classified as Likely benign.
Frequency
Consequence
NM_001376.5 synonymous
Scores
Clinical Significance
Conservation
Publications
- autosomal dominant childhood-onset proximal spinal muscular atrophy without contracturesInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp
- intellectual disability, autosomal dominant 13Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
- neuronopathy, distal hereditary motorInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- Charcot-Marie-Tooth disease axonal type 2OInheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- autosomal dominant non-syndromic intellectual disabilityInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Benign. The variant received -13 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00252 AC: 384AN: 152138Hom.: 3 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000569 AC: 143AN: 251274 AF XY: 0.000361 show subpopulations
GnomAD4 exome AF: 0.000231 AC: 337AN: 1461884Hom.: 2 Cov.: 32 AF XY: 0.000173 AC XY: 126AN XY: 727242 show subpopulations
GnomAD4 genome AF: 0.00252 AC: 383AN: 152256Hom.: 3 Cov.: 32 AF XY: 0.00224 AC XY: 167AN XY: 74450 show subpopulations
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:3
- -
- -
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
- -
Charcot-Marie-Tooth disease axonal type 2O Benign:1
- -
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. -
not provided Benign:1
DYNC1H1: BP4, BP7, BS1 -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at