Variant chr3-159764810-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014575.4(SCHIP1):c.431C>T(p.Pro144Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000455 in 1,428,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P144S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

SCHIP1
NM_014575.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.680

Variant links:

Genes affected

SCHIP1 (HGNC:):

SCHIP1 links:

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ACMG classification

Classification made for transcript

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=0.18945068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCHIP1	NM_014575.4 linkuse as main transcript	c.431C>T	p.Pro144Leu	missense_variant	2/8	ENST00000638749.2
IQCJ-SCHIP1	NM_001197113.2 linkuse as main transcript	c.659C>T	p.Pro220Leu	missense_variant	5/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000269

AC:

AN:

185988

Hom.:

AF XY:

0.0000195

AC XY:

AN XY:

102488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000330

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000522

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000455

AC:

AN:

1428412

Hom.:

Cov.:

AF XY:

0.0000339

AC XY:

AN XY:

707840

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

Gnomad4 AMR exome

AF:

0.0000242

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000501

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000678

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000260

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.659C>T (p.P220L) alteration is located in exon 5 (coding exon 5) of the IQCJ-SCHIP1 gene. This alteration results from a C to T substitution at nucleotide position 659, causing the proline (P) at amino acid position 220 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

.;T;.;.;.;.;.

Eigen

Benign

0.070

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.71

T;T;T;T;T;T;T

M_CAP

Pathogenic

0.57

MetaRNN

Benign

0.19

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.5

N;N;.;N;.;N;.

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;D;.;D;.;D;.

Sift4G

Uncertain

0.0090

D;D;.;T;.;T;.

Polyphen

0.80

.;.;.;.;.;P;.

Vest4

0.22

MutPred

0.13

.;.;Loss of glycosylation at P145 (P = 0.017);Loss of glycosylation at P145 (P = 0.017);.;.;.;

MVP

0.14

MPC

0.32

ClinPred

0.18

GERP RS

4.8

Varity_R

0.19

gMVP

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over