chr11-6615200-C-T
Variant summary
Our verdict is Benign. The variant received -16 ACMG points: 4P and 20B. PM1PM5BP4_StrongBP6_Very_StrongBS1BS2
The NM_000391.4(TPP1):c.1396G>A(p.Val466Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,614,178 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V466G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000391.4 missense
Scores
Clinical Significance
Conservation
Publications
- neuronal ceroid lipofuscinosisInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- neuronal ceroid lipofuscinosis 2Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Myriad Women’s Health, G2P, Orphanet
- autosomal recessive spinocerebellar ataxia 7Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Benign. The variant received -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00312 AC: 475AN: 152166Hom.: 3 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.000787 AC: 198AN: 251490 AF XY: 0.000567 show subpopulations
GnomAD4 exome AF: 0.000324 AC: 474AN: 1461894Hom.: 3 Cov.: 34 AF XY: 0.000282 AC XY: 205AN XY: 727248 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00315 AC: 479AN: 152284Hom.: 4 Cov.: 32 AF XY: 0.00289 AC XY: 215AN XY: 74458 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Benign:2
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not specified Benign:1
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. -
Inborn genetic diseases Benign:1
This alteration is classified as 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. -
Neuronal ceroid lipofuscinosis 2 Benign:1
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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at