chr22-41909827-C-G

Variant names:

• chr22-41909827-C-G
• NM_001207020.3:c.1132G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001207020.3(SHISA8):​c.1132G>C​(p.Gly378Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SHISA8 NM_001207020.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.809

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078558534).
• BP6: Variant 22-41909827-C-G is Benign according to our data. Variant chr22-41909827-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2548931.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHISA8	NM_001207020.3	c.1132G>C	p.Gly378Arg	missense_variant	Exon 4 of 4	ENST00000621082.2	NP_001193949.1
SHISA8	NM_001353438.2	c.1417G>C	p.Gly473Arg	missense_variant	Exon 4 of 4		NP_001340367.1
SHISA8	NM_001353439.2	c.1309G>C	p.Gly437Arg	missense_variant	Exon 4 of 4		NP_001340368.1
SHISA8	XM_006724256.5	c.1297G>C	p.Gly433Arg	missense_variant	Exon 4 of 4		XP_006724319.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHISA8	ENST00000621082.2	c.1132G>C	p.Gly378Arg	missense_variant	Exon 4 of 4	5	NM_001207020.3	ENSP00000481203.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

May 18, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.41
DANN	Benign	0.55
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.079	T
PrimateAI	Uncertain	0.51	T
Sift4G	Benign	0.40	T
Vest4		0.058
MVP		0.39
GERP RS		-7.6
Varity_R		0.056
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-42305831;