1-2512988-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_018216.4(PANK4):c.1627C>T(p.Arg543Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,611,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 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. R543H) has been classified as Uncertain significance.
Frequency
Consequence
NM_018216.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PANK4 | NM_018216.4 | c.1627C>T | p.Arg543Cys | missense_variant | 13/19 | ENST00000378466.9 | NP_060686.3 | |
PANK4 | XM_047424306.1 | c.1186C>T | p.Arg396Cys | missense_variant | 13/19 | XP_047280262.1 | ||
PANK4 | XR_241034.4 | n.1636C>T | non_coding_transcript_exon_variant | 13/17 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152244Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000401 AC: 10AN: 249350Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 135130
GnomAD4 exome AF: 0.000124 AC: 181AN: 1459198Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 88AN XY: 725712
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152244Hom.: 0 Cov.: 34 AF XY: 0.0000134 AC XY: 1AN XY: 74384
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 14, 2023 | The c.1627C>T (p.R543C) alteration is located in exon 13 (coding exon 13) of the PANK4 gene. This alteration results from a C to T substitution at nucleotide position 1627, causing the arginine (R) at amino acid position 543 to be replaced by a cysteine (C). 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