chr3-159764647-G-A

Position:

• chr3-159764647-G-A

Variant summary

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

The NM_014575.4(SCHIP1):​c.268G>A​(p.Asp90Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCHIP1 NM_014575.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23

Genes affected

SCHIP1 (HGNC:):

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=0.2040343).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCHIP1	NM_014575.4	c.268G>A	p.Asp90Asn	missense_variant	2/8	ENST00000638749.2
IQCJ-SCHIP1	NM_001197113.2	c.496G>A	p.Asp166Asn	missense_variant	5/11

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.496G>A (p.D166N) alteration is located in exon 5 (coding exon 5) of the IQCJ-SCHIP1 gene. This alteration results from a G to A substitution at nucleotide position 496, causing the aspartic acid (D) at amino acid position 166 to be replaced by an asparagine (N). 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	0.089
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	.;T;.;.;.;.;.;.
Eigen	Benign	-0.0097
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.73	T;T;T;T;T;T;T;T
M_CAP	Benign	0.060	D
MetaRNN	Benign	0.20	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.94	D;D;D;D;D;D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.3	N;N;.;.;N;.;N;.
REVEL	Benign	0.074
Sift	Uncertain	0.0080	D;D;.;.;D;.;D;.
Sift4G	Benign	0.14	T;T;.;.;T;.;T;.
Polyphen		0.42	.;.;.;.;.;.;B;.
Vest4		0.20
MutPred		0.14		.;.;.;Gain of helix (P = 0.062);Gain of helix (P = 0.062);.;.;.;
MVP		0.11
MPC		1.0
ClinPred		0.88	D
GERP RS		3.9
Varity_R		0.094
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr3-159482436;