chr1-116384015-T-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_000701.8(ATP1A1):c.14T>C(p.Val5Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V5F) has been classified as Likely benign.
Frequency
Consequence
NM_000701.8 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATP1A1 | NM_000701.8 | c.14T>C | p.Val5Ala | missense_variant, splice_region_variant | 2/23 | ENST00000295598.10 | |
ATP1A1 | NM_001160233.2 | c.14T>C | p.Val5Ala | missense_variant, splice_region_variant | 2/23 | ||
ATP1A1 | NM_001160234.2 | c.-80T>C | splice_region_variant, 5_prime_UTR_variant | 2/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATP1A1 | ENST00000295598.10 | c.14T>C | p.Val5Ala | missense_variant, splice_region_variant | 2/23 | 1 | NM_000701.8 | P4 | |
ATP1A1-AS1 | ENST00000675607.1 | n.386-3970A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251224Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135772
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461478Hom.: 0 Cov.: 30 AF XY: 0.00000963 AC XY: 7AN XY: 727040
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 26, 2023 | The c.14T>C (p.V5A) alteration is located in exon 2 (coding exon 2) of the ATP1A1 gene. This alteration results from a T to C substitution at nucleotide position 14, causing the valine (V) at amino acid position 5 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2023 | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 5 of the ATP1A1 protein (p.Val5Ala). This variant is present in population databases (rs780694923, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with ATP1A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1364803). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at