Variant chr1-160092564-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_052868.6(IGSF8):c.1444G>A(p.Glu482Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000686 in 1,458,254 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

IGSF8
NM_052868.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

IGSF8 (HGNC:17813): (immunoglobulin superfamily member 8) This gene encodes a member the EWI subfamily of the immunoglobulin protein superfamily. Members of this family contain a single transmembrane domain, an EWI (Glu-Trp-Ile)-motif and a variable number of immunoglobulin domains. This protein interacts with the tetraspanins CD81 and CD9 and may regulate their role in certain cellular functions including cell migration and viral infection. The encoded protein may also function as a tumor suppressor by inhibiting the proliferation of certain cancers. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

IGSF8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGSF8	NM_052868.6 linkuse as main transcript	c.1444G>A	p.Glu482Lys	missense_variant	5/7	ENST00000314485.12	NP_443100.1	Q969P0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGSF8	ENST00000314485.12 linkuse as main transcript	c.1444G>A	p.Glu482Lys	missense_variant	5/7	1	NM_052868.6	ENSP00000316664.7	Q969P0-1
IGSF8	ENST00000368086.5 linkuse as main transcript	c.1444G>A	p.Glu482Lys	missense_variant	5/7	1		ENSP00000357065.1	Q969P0-1
IGSF8	ENST00000614243.4 linkuse as main transcript	c.1444G>A	p.Glu482Lys	missense_variant	6/8	1		ENSP00000477565.1	Q969P0-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000207

AC:

AN:

241674

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

132214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000686

AC:

AN:

1458254

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

725600

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Feb 17, 2024

The c.1444G>A (p.E482K) alteration is located in exon 5 (coding exon 5) of the IGSF8 gene. This alteration results from a G to A substitution at nucleotide position 1444, causing the glutamic acid (E) at amino acid position 482 to be replaced by a lysine (K). 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

0.20

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

T;T;T

Eigen

Benign

-0.085

Eigen_PC

Benign

-0.072

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.82

.;.;T

M_CAP

Benign

0.0068

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;M

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.71

N;N;.

REVEL

Benign

0.077

Sift

Benign

0.28

T;T;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.89

P;P;P

Vest4

0.64

MutPred

0.49

Gain of methylation at E482 (P = 0.0022);Gain of methylation at E482 (P = 0.0022);Gain of methylation at E482 (P = 0.0022);

MVP

0.22

MPC

0.65

ClinPred

0.38

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.091

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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