rs758816689

Variant names:

• chr3-52455654-C-A
• NM_007184.4:c.13C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-52455654-C-A
• chr3-52455654-C-G
• chr3-52455654-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007184.4(NISCH):​c.13C>A​(p.Arg5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000838 in 1,192,664 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: 31)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: NISCH NM_007184.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08362654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NISCH	NM_007184.4	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 21	ENST00000345716.9	NP_009115.3
NISCH	NM_001276293.2	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 13		NP_001263222.2
NISCH	NM_001276294.2	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 14		NP_001263223.2
NISCH	XM_047447373.1	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 18		XP_047303329.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NISCH	ENST00000345716.9	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 21	1	NM_007184.4	ENSP00000339958.4
NISCH	ENST00000479054.5	c.13C>A	p.Arg5Ser	missense_variant	Exon 2 of 22	1		ENSP00000418232.1
NISCH	ENST00000488380.5	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 13	1		ENSP00000417812.1
NISCH	ENST00000420808.2	c.13C>A	p.Arg5Ser	missense_variant	Exon 1 of 14	5		ENSP00000392484.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.38e-7 AC: 1 AN: 1192664 Hom.: 0 Cov.: 31 AF XY: 0.00000173 AC XY: 1 AN XY: 577832

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000557

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.042	T;T;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.70	.;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.084	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;N;.;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.40	N;N;N;N
REVEL	Benign	0.060
Sift	Uncertain	0.028	D;D;D;T
Sift4G	Benign	0.068	T;T;T;T
Polyphen		0.010	B;B;B;.
Vest4		0.17
MutPred		0.23		Loss of methylation at T5 (P = 0.0439);Loss of methylation at T5 (P = 0.0439);Loss of methylation at T5 (P = 0.0439);Loss of methylation at T5 (P = 0.0439);
MVP		0.082
MPC		0.50
ClinPred		0.12	T
GERP RS		0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-52489670;