dbSNP rs1020459397: SHISA8:p.Leu302Phe (chr22-41910053-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001207020.3(SHISA8):c.906G>C(p.Leu302Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000496 in 1,255,012 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00048 ( 1 hom. )

Consequence

SHISA8
NM_001207020.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.054276496).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SHISA8	NM_001207020.3	MANE Select	c.906G>C	p.Leu302Phe	missense	Exon 4 of 4	NP_001193949.1	B8ZZ34-1
SHISA8	NM_001353438.2		c.1191G>C	p.Leu397Phe	missense	Exon 4 of 4	NP_001340367.1	B8ZZ34-3
SHISA8	NM_001353439.2		c.1083G>C	p.Leu361Phe	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.906G>C	p.Leu302Phe	missense	Exon 4 of 4	ENSP00000481203.1	B8ZZ34-1

Frequencies

GnomAD3 genomes

AF:

0.000606

AC:

AN:

151814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00390

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000692

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.00

AC:

AN:

AF XY:

0.00

Gnomad NFE exome

AF:

0.00

GnomAD4 exome

AF:

0.000480

AC:

530

AN:

1103090

Hom.:

Cov.:

AF XY:

0.000477

AC XY:

250

AN XY:

523660

show subpopulations

African (AFR)

AF:

0.0000440

AC:

AN:

22728

American (AMR)

AF:

0.00

AC:

AN:

8262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14412

East Asian (EAS)

AF:

0.00

AC:

AN:

26184

South Asian (SAS)

AF:

0.00

AC:

AN:

23854

European-Finnish (FIN)

AF:

0.00375

AC:

AN:

22666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3006

European-Non Finnish (NFE)

AF:

0.000455

AC:

426

AN:

937164

Other (OTH)

AF:

0.000402

AC:

AN:

44814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

130

162

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000606

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.000660

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41508

American (AMR)

AF:

0.0000655

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00390

AC:

AN:

10504

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000692

AC:

AN:

67886

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.000298

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.42

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.50

MetaRNN

Benign

0.054

PhyloP100

1.2

PrimateAI

Pathogenic

0.86

Sift4G

Uncertain

0.041

Vest4

0.098

MVP

0.24

GERP RS

3.0

Varity_R

0.055

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over