12-57225503-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_007224.4(NXPH4):c.683C>T(p.Ser228Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,610,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S228A) has been classified as Uncertain significance.
Frequency
Consequence
NM_007224.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NXPH4 | ENST00000349394.6 | c.683C>T | p.Ser228Leu | missense_variant | Exon 2 of 2 | 1 | NM_007224.4 | ENSP00000333593.6 | ||
NXPH4 | ENST00000556415.1 | n.*810C>T | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 | ENSP00000452288.1 | ||||
NXPH4 | ENST00000556415.1 | n.*810C>T | 3_prime_UTR_variant | Exon 3 of 3 | 2 | ENSP00000452288.1 | ||||
NXPH4 | ENST00000555154.1 | n.*84C>T | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152072Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239480Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 131020
GnomAD4 exome AF: 0.00000549 AC: 8AN: 1458454Hom.: 0 Cov.: 47 AF XY: 0.00000551 AC XY: 4AN XY: 725476
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74394
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.683C>T (p.S228L) alteration is located in exon 2 (coding exon 2) of the NXPH4 gene. This alteration results from a C to T substitution at nucleotide position 683, causing the serine (S) at amino acid position 228 to be replaced by a leucine (L). 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