chr1-2508954-G-A
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_018216.4(PANK4):c.2215C>T(p.Arg739Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,609,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 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. R739H) has been classified as Uncertain significance.
Frequency
Consequence
NM_018216.4 missense
Scores
Clinical Significance
Conservation
Publications
- early-onset posterior polar cataractInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- cataractInheritance: AD Classification: LIMITED Submitted by: G2P
- cataract 49Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Our verdict: Benign. The variant received -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PANK4 | ENST00000378466.9 | c.2215C>T | p.Arg739Cys | missense_variant | Exon 19 of 19 | 1 | NM_018216.4 | ENSP00000367727.5 | ||
PANK4 | ENST00000435556.8 | c.2098C>T | p.Arg700Cys | missense_variant | Exon 19 of 19 | 2 | ENSP00000421433.3 | |||
PANK4 | ENST00000505228.5 | n.*333C>T | non_coding_transcript_exon_variant | Exon 16 of 16 | 5 | ENSP00000425932.1 | ||||
PANK4 | ENST00000505228.5 | n.*333C>T | 3_prime_UTR_variant | Exon 16 of 16 | 5 | ENSP00000425932.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152014Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00000822 AC: 2AN: 243438 AF XY: 0.00000755 show subpopulations
GnomAD4 exome AF: 0.00000412 AC: 6AN: 1457152Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 4AN XY: 724842 show subpopulations
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152014Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74238 show subpopulations
ClinVar
Submissions by phenotype
not specified 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at