1-2512976-C-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_018216.4(PANK4):c.1639G>T(p.Ala547Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. 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. A547V) has been classified as Benign.
Frequency
Consequence
NM_018216.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PANK4 | NM_018216.4 | c.1639G>T | p.Ala547Ser | missense_variant | 13/19 | ENST00000378466.9 | NP_060686.3 | |
PANK4 | XM_047424306.1 | c.1198G>T | p.Ala400Ser | missense_variant | 13/19 | XP_047280262.1 | ||
PANK4 | XR_241034.4 | n.1648G>T | non_coding_transcript_exon_variant | 13/17 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152258Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249872Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135434
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1459840Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 726208
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152258Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74384
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 08, 2023 | The c.1639G>T (p.A547S) alteration is located in exon 13 (coding exon 13) of the PANK4 gene. This alteration results from a G to T substitution at nucleotide position 1639, causing the alanine (A) at amino acid position 547 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at