17-74748890-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_004252.5(NHERF1):c.44G>T(p.Cys15Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004252.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NHERF1 | ENST00000262613.10 | c.44G>T | p.Cys15Phe | missense_variant | Exon 1 of 6 | 1 | NM_004252.5 | ENSP00000262613.5 | ||
NHERF1 | ENST00000583369.5 | c.44G>T | p.Cys15Phe | missense_variant | Exon 1 of 3 | 3 | ENSP00000464321.1 | |||
SLC9A3R1-AS1 | ENST00000585285.1 | n.23C>A | non_coding_transcript_exon_variant | Exon 1 of 2 | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000447 AC: 1AN: 223760Hom.: 0 AF XY: 0.00000805 AC XY: 1AN XY: 124244
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.92e-7 AC: 1AN: 1446022Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1AN XY: 718980
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant has not been reported in the literature in individuals with SLC9A3R1-related conditions. This sequence change replaces cysteine with phenylalanine at codon 15 of the SLC9A3R1 protein (p.Cys15Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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