NM_001207020.3:c.1132G>C

Variant names:

• chr22-41909827-C-G
• rs2077534934
• NM_001207020.3:c.1132G>C

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 2548931.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001207020.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA8	NM_001207020.3	MANE Select	c.1132G>C	p.Gly378Arg	missense	Exon 4 of 4	NP_001193949.1	B8ZZ34-1
	SHISA8	NM_001353438.2		c.1417G>C	p.Gly473Arg	missense	Exon 4 of 4	NP_001340367.1	B8ZZ34-3
	SHISA8	NM_001353439.2		c.1309G>C	p.Gly437Arg	missense	Exon 4 of 4	NP_001340368.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA8	ENST00000621082.2	TSL:5 MANE Select	c.1132G>C	p.Gly378Arg	missense	Exon 4 of 4	ENSP00000481203.1	B8ZZ34-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.81
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

Other links and lift over

dbSNP: rs2077534934; hg19: chr22-42305831;