Variant chr22-41910537-T-G 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_001207020.3(SHISA8):c.682A>C(p.Asn228His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000622 in 1,238,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000062 ( 0 hom. )

Consequence

SHISA8
NM_001207020.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.939

Variant links:

Genes affected

SHISA8 (HGNC:18351): (shisa family member 8) Predicted to be involved in regulation of AMPA receptor activity and regulation of short-term neuronal synaptic plasticity. Predicted to be integral component of membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in dendritic spine membrane; postsynaptic density; and postsynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

SHISA8 links:

Genome browser will be placed here

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=0.17351219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SHISA8	NM_001207020.3 linkuse as main transcript	c.682A>C	p.Asn228His	missense_variant	3/4	ENST00000621082.2
SHISA8	NM_001353438.2 linkuse as main transcript	c.967A>C	p.Asn323His	missense_variant	3/4
SHISA8	NM_001353439.2 linkuse as main transcript	c.859A>C	p.Asn287His	missense_variant	3/4
SHISA8	XM_006724256.5 linkuse as main transcript	c.847A>C	p.Asn283His	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHISA8	ENST00000621082.2 linkuse as main transcript	c.682A>C	p.Asn228His	missense_variant	3/4	5	NM_001207020.3	P1	B8ZZ34-1

Frequencies

GnomAD3 genomes

AF:

0.0000660

AC:

AN:

151626

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00318

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000617

AC:

AN:

1086588

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

516966

show subpopulations

Gnomad4 AFR exome

AF:

0.000178

Gnomad4 AMR exome

AF:

0.000249

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000445

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000475

Gnomad4 OTH exome

AF:

0.000231

GnomAD4 genome

AF:

0.0000660

AC:

AN:

151626

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

74028

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000113

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

Jan 31, 2024

The c.682A>C (p.N228H) alteration is located in exon 3 (coding exon 3) of the SHISA8 gene. This alteration results from a A to C substitution at nucleotide position 682, causing the asparagine (N) at amino acid position 228 to be replaced by a histidine (H). 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

0.094

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.67

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.46

MetaRNN

Benign

0.17

PrimateAI

Uncertain

0.55

Sift4G

Benign

0.073

Vest4

0.20

MVP

0.30

GERP RS

3.5

Varity_R

0.12

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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