NM_004252.5:c.81C>T
Variant names:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2
The NM_004252.5(NHERF1):c.81C>T(p.His27His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,450,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
NHERF1
NM_004252.5 synonymous
NM_004252.5 synonymous
Scores
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.09
Genes affected
NHERF1 (HGNC:11075): (NHERF family PDZ scaffold protein 1) This gene encodes a sodium/hydrogen exchanger regulatory cofactor. The protein interacts with and regulates various proteins including the cystic fibrosis transmembrane conductance regulator and G-protein coupled receptors such as the beta2-adrenergic receptor and the parathyroid hormone 1 receptor. The protein also interacts with proteins that function as linkers between integral membrane and cytoskeletal proteins. The protein localizes to actin-rich structures including membrane ruffles, microvilli, and filopodia. Mutations in this gene result in hypophosphatemic nephrolithiasis/osteoporosis type 2, and loss of heterozygosity of this gene is implicated in breast cancer.[provided by RefSeq, Sep 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP7
Synonymous conserved (PhyloP=1.1 with no splicing effect.
BS2
High AC in GnomAdExome4 at 9 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NHERF1 | ENST00000262613.10 | c.81C>T | p.His27His | synonymous_variant | Exon 1 of 6 | 1 | NM_004252.5 | ENSP00000262613.5 | ||
NHERF1 | ENST00000583369.5 | c.81C>T | p.His27His | synonymous_variant | Exon 1 of 3 | 3 | ENSP00000464321.1 | |||
SLC9A3R1-AS1 | ENST00000585285.1 | n.-15G>A | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000440 AC: 1AN: 227074Hom.: 0 AF XY: 0.00000796 AC XY: 1AN XY: 125632
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GnomAD4 exome AF: 0.00000620 AC: 9AN: 1450896Hom.: 0 Cov.: 32 AF XY: 0.0000111 AC XY: 8AN XY: 721640
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GnomAD4 genome Cov.: 33
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33
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at