rs769816246

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004252.5(NHERF1):​c.8C>G​(p.Ala3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 1,440,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
Exomes š‘“: 0.0000090 ( 0 hom. )

Consequence

NHERF1
NM_004252.5 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08
Variant links:
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]
SLC9A3R1-AS1 (HGNC:55322): (SLC9A3R1 antisense RNA 1)
MIR3615 (HGNC:38905): (microRNA 3615) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.067008585).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NHERF1NM_004252.5 linkc.8C>G p.Ala3Gly missense_variant Exon 1 of 6 ENST00000262613.10 NP_004243.1 O14745-1
SLC9A3R1-AS1NR_187307.1 linkn.879G>C non_coding_transcript_exon_variant Exon 2 of 3
MIR3615NR_037409.1 linkn.*155C>G downstream_gene_variant
MIR3615unassigned_transcript_3091 n.*171C>G downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NHERF1ENST00000262613.10 linkc.8C>G p.Ala3Gly missense_variant Exon 1 of 6 1 NM_004252.5 ENSP00000262613.5 O14745-1
NHERF1ENST00000583369.5 linkc.8C>G p.Ala3Gly missense_variant Exon 1 of 3 3 ENSP00000464321.1 J3QRP6
SLC9A3R1-AS1ENST00000585285.1 linkn.59G>C non_coding_transcript_exon_variant Exon 1 of 2 3
MIR3615ENST00000581999.1 linkn.*155C>G downstream_gene_variant 6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000425
AC:
9
AN:
211734
Hom.:
0
AF XY:
0.0000338
AC XY:
4
AN XY:
118262
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000271
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000902
AC:
13
AN:
1440476
Hom.:
0
Cov.:
31
AF XY:
0.00000838
AC XY:
6
AN XY:
716218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000205
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000271
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.0000339
AC:
4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
23
DANN
Benign
0.95
DEOGEN2
Benign
0.015
T;T
Eigen
Benign
-0.0028
Eigen_PC
Benign
0.087
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.056
D
MetaRNN
Benign
0.067
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.69
.;N
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-0.15
.;N
REVEL
Benign
0.036
Sift
Benign
0.032
.;D
Sift4G
Uncertain
0.047
D;T
Polyphen
0.73
.;P
Vest4
0.29
MutPred
0.28
Loss of stability (P = 0.0745);Loss of stability (P = 0.0745);
MVP
0.63
MPC
1.1
ClinPred
0.20
T
GERP RS
4.3
Varity_R
0.095
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs769816246; hg19: chr17-72744993; API