rs147937807
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_007184.4(NISCH):āc.713C>Gā(p.Ser238Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,266 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.9e-7 ( 0 hom. )
Consequence
NISCH
NM_007184.4 missense
NM_007184.4 missense
Scores
11
8
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.81
Genes affected
NISCH (HGNC:18006): (nischarin) This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the cytosol and anchors to the inner layer of the plasma membrane. The orthologous mouse protein has been shown to influence cytoskeletal organization and cell migration by binding to alpha-5-beta-1 integrin. In humans, this protein has been shown to bind to the adapter insulin receptor substrate 4 (IRS4) to mediate translocation of alpha-5 integrin from the cell membrane to endosomes. Expression of this protein was reduced in human breast cancers while its overexpression reduced tumor growth and metastasis; possibly by limiting the expression of alpha-5 integrin. In human cardiac tissue, this gene was found to affect cell growth and death while in neural tissue it affected neuronal growth and differentiation. Alternative splicing results in multiple transcript variants encoding differerent isoforms. Some isoforms lack the expected C-terminal domains of a functional imidazoline receptor. [provided by RefSeq, Jan 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| NISCH | NM_007184.4 | c.713C>G | p.Ser238Trp | missense_variant | Exon 7 of 21 | ENST00000345716.9 | NP_009115.3 | |
| NISCH | NM_001276293.2 | c.713C>G | p.Ser238Trp | missense_variant | Exon 7 of 13 | NP_001263222.2 | ||
| NISCH | NM_001276294.2 | c.713C>G | p.Ser238Trp | missense_variant | Exon 7 of 14 | NP_001263223.2 | ||
| NISCH | XM_047447373.1 | c.713C>G | p.Ser238Trp | missense_variant | Exon 7 of 18 | XP_047303329.1 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457266Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 723906
GnomAD4 exome
AF:
AC:
1
AN:
1457266
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
723906
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Benign
T;T;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);Gain of MoRF binding (P = 0.0273);
MVP
MPC
1.5
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.