chr22-41909929-C-T

Variant names:

• chr22-41909929-C-T
• NM_001207020.3:c.1030G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001207020.3(SHISA8):​c.1030G>A​(p.Ala344Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000073 in 1,369,002 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: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: SHISA8 NM_001207020.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.306
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095604).

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.1030G>A	p.Ala344Thr	missense	Exon 4 of 4	NP_001193949.1	B8ZZ34-1
	SHISA8	NM_001353438.2		c.1315G>A	p.Ala439Thr	missense	Exon 4 of 4	NP_001340367.1	B8ZZ34-3
	SHISA8	NM_001353439.2		c.1207G>A	p.Ala403Thr	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.1030G>A	p.Ala344Thr	missense	Exon 4 of 4	ENSP00000481203.1	B8ZZ34-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.30e-7 AC: 1 AN: 1369002 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 674890

African (AFR) AF: 0.00 AC: 0 AN: 30174

American (AMR) AF: 0.00 AC: 0 AN: 34248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24790

East Asian (EAS) AF: 0.00 AC: 0 AN: 34224

South Asian (SAS) AF: 0.00 AC: 0 AN: 77148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5192

European-Non Finnish (NFE) AF: 9.32e-7 AC: 1 AN: 1072632

Other (OTH) AF: 0.00 AC: 0 AN: 57208

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.075
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.78
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.47	T
MetaRNN	Benign	0.096	T
PhyloP100		0.31
PrimateAI	Uncertain	0.76	T
Sift4G	Benign	0.71	T
Vest4		0.048
MVP		0.18
GERP RS		-0.36
Varity_R		0.020
gMVP		0.23

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

hg19: chr22-42305933;