NM_014575.4:c.353C>T

Variant names:

• chr3-159764732-C-T
• NM_014575.4:c.353C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014575.4(SCHIP1):​c.353C>T​(p.Pro118Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000352 in 1,420,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SCHIP1 NM_014575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.965
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17598587).

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.353C>T	p.Pro118Leu	missense	Exon 2 of 8	NP_055390.1	P0DPB3-1
	IQCJ-SCHIP1	NM_001197113.2		c.581C>T	p.Pro194Leu	missense	Exon 5 of 11	NP_001184042.1	B3KU38-1
	IQCJ-SCHIP1	NM_001197114.2		c.500C>T	p.Pro167Leu	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.353C>T	p.Pro118Leu	missense	Exon 2 of 8	ENSP00000491030.1	P0DPB3-1
	IQCJ-SCHIP1	ENST00000485419.7	TSL:2	c.581C>T	p.Pro194Leu	missense	Exon 5 of 11	ENSP00000420182.1	B3KU38-1
	SCHIP1	ENST00000412423.8	TSL:1	c.353C>T	p.Pro118Leu	missense	Exon 2 of 8	ENSP00000400942.2	P0DPB3-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000352 AC: 5 AN: 1420890 Hom.: 0 Cov.: 31 AF XY: 0.00000427 AC XY: 3 AN XY: 703014

African (AFR) AF: 0.00 AC: 0 AN: 32260

American (AMR) AF: 0.0000253 AC: 1 AN: 39602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24948

East Asian (EAS) AF: 0.00 AC: 0 AN: 37292

South Asian (SAS) AF: 0.00 AC: 0 AN: 80684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5508

European-Non Finnish (NFE) AF: 0.00000366 AC: 4 AN: 1092846

Other (OTH) AF: 0.00 AC: 0 AN: 58862

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0096	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.025
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.96
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.096
Sift	Benign	0.35	T
Sift4G	Benign	0.33	T
Polyphen		0.65	P
Vest4		0.41
MutPred		0.17		Gain of glycosylation at S117 (P = 0.0067)
MVP		0.12
MPC		0.36
ClinPred		0.19	T
GERP RS		3.1
PromoterAI		-0.023	Neutral
Varity_R		0.093
gMVP		0.12
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

hg19: chr3-159482521;