3-159764729-C-T

Variant names:

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

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>T​(p.Ser117Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 1,573,732 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: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SCHIP1 NM_014575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.06204447).

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>T	p.Ser117Phe	missense	Exon 2 of 8	NP_055390.1	P0DPB3-1
	IQCJ-SCHIP1	NM_001197113.2		c.578C>T	p.Ser193Phe	missense	Exon 5 of 11	NP_001184042.1	B3KU38-1
	IQCJ-SCHIP1	NM_001197114.2		c.497C>T	p.Ser166Phe	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>T	p.Ser117Phe	missense	Exon 2 of 8	ENSP00000491030.1	P0DPB3-1
	IQCJ-SCHIP1	ENST00000485419.7	TSL:2	c.578C>T	p.Ser193Phe	missense	Exon 5 of 11	ENSP00000420182.1	B3KU38-1
	SCHIP1	ENST00000412423.8	TSL:1	c.350C>T	p.Ser117Phe	missense	Exon 2 of 8	ENSP00000400942.2	P0DPB3-2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1421602 Hom.: 0 Cov.: 31 AF XY: 0.00000142 AC XY: 1 AN XY: 703436

African (AFR) AF: 0.0000310 AC: 1 AN: 32282

American (AMR) AF: 0.00 AC: 0 AN: 39644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24920

East Asian (EAS) AF: 0.00 AC: 0 AN: 37380

South Asian (SAS) AF: 0.00 AC: 0 AN: 80712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5498

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093222

Other (OTH) AF: 0.00 AC: 0 AN: 58866

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152130 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74326

African (AFR) AF: 0.0000724 AC: 3 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000868 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.00000835 AC: 1

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	0.070
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.41	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.31
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.094
Sift	Benign	0.036	D
Sift4G	Benign	0.087	T
Polyphen		0.0	B
Vest4		0.19
MVP		0.043
MPC		0.40
ClinPred		0.081	T
GERP RS		4.1
PromoterAI		0.092	Neutral
Varity_R		0.046
gMVP		0.16
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;