3-159764729-C-G

Variant names:

• chr3-159764729-C-G
• rs762357345
• NM_014575.4:c.350C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014575.4(SCHIP1):​c.350C>G​(p.Ser117Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S117F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCHIP1 NM_014575.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 0 publications found

Genes affected

SCHIP1 (HGNC:15678): (schwannomin interacting protein 1) Enables identical protein binding activity. Predicted to be involved in positive regulation of hippo signaling. Predicted to act upstream of or within several processes, including animal organ development; face morphogenesis; and fibroblast migration. Located in several cellular components, including cell junction; cytosol; and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

IQCJ-SCHIP1 (HGNC:38842): (IQCJ-SCHIP1 readthrough) This locus represents naturally occurring read-through transcription from the neighboring IQ motif containing J (IQCJ) and schwannomin interacting protein 1 (SCHIP1) genes. Alternative splicing results in multiple transcript variants that are composed of in-frame exons from each individual gene. The resulting fusion products are thought to be components of the multimolecular complexes of axon initial segments and nodes of Ranvier, and they may play a role in calcium-mediated responses. [provided by RefSeq, Oct 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.041313678).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014575.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCHIP1	NM_014575.4	MANE Select	c.350C>G	p.Ser117Cys	missense	Exon 2 of 8	NP_055390.1	P0DPB3-1
	IQCJ-SCHIP1	NM_001197113.2		c.578C>G	p.Ser193Cys	missense	Exon 5 of 11	NP_001184042.1	B3KU38-1
	IQCJ-SCHIP1	NM_001197114.2		c.497C>G	p.Ser166Cys	missense	Exon 4 of 10	NP_001184043.1	B3KU38-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCHIP1	ENST00000638749.2	TSL:1 MANE Select	c.350C>G	p.Ser117Cys	missense	Exon 2 of 8	ENSP00000491030.1	P0DPB3-1
	IQCJ-SCHIP1	ENST00000485419.7	TSL:2	c.578C>G	p.Ser193Cys	missense	Exon 5 of 11	ENSP00000420182.1	B3KU38-1
	SCHIP1	ENST00000412423.8	TSL:1	c.350C>G	p.Ser117Cys	missense	Exon 2 of 8	ENSP00000400942.2	P0DPB3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.036
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.0025	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.16	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.31
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.31	N
REVEL	Benign	0.089
Sift	Benign	1.0	T
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.18		Gain of glycosylation at S117 (P = 0.0067)
MVP		0.043
MPC		0.30
ClinPred		0.061	T
GERP RS		4.1
PromoterAI		-0.070	Neutral
Varity_R		0.050
gMVP		0.11
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs762357345; hg19: chr3-159482518;