chr3-48479217-C-T

Variant names:

• chr3-48479217-C-T
• rs1473018571
• NM_016479.6:c.274G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016479.6(SHISA5):​c.274G>A​(p.Ala92Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000566 in 1,413,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: SHISA5 NM_016479.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.862
• Publications: 1 publications found

Genes affected

SHISA5 (HGNC:30376): (shisa family member 5) This gene encodes a member of the shisa family. The encoded protein is localized to the endoplasmic reticulum, and together with p53 induces apoptosis in a caspase-dependent manner. Alternative splicing results in multiple transcript variants. Related pseudogenes of this gene are found on chromosome X. [provided by RefSeq, Apr 2016]

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=0.054060012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016479.6. 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
	SHISA5	NM_016479.6	MANE Select	c.274G>A	p.Ala92Thr	missense	Exon 3 of 6	NP_057563.3
	SHISA5	NM_001272065.3		c.253G>A	p.Ala85Thr	missense	Exon 3 of 6	NP_001258994.1	Q8N114-5
	SHISA5	NM_001272066.2		c.181G>A	p.Ala61Thr	missense	Exon 3 of 6	NP_001258995.1	Q8N114-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHISA5	ENST00000296444.7	TSL:1 MANE Select	c.274G>A	p.Ala92Thr	missense	Exon 3 of 6	ENSP00000296444.2	Q8N114-1
	SHISA5	ENST00000949300.1		c.274G>A	p.Ala92Thr	missense	Exon 3 of 6	ENSP00000619359.1
	SHISA5	ENST00000929322.1		c.274G>A	p.Ala92Thr	missense	Exon 3 of 6	ENSP00000599381.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 236198 AF XY: 0.0000233

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000566 AC: 8 AN: 1413102 Hom.: 0 Cov.: 31 AF XY: 0.00000998 AC XY: 7 AN XY: 701556

African (AFR) AF: 0.00 AC: 0 AN: 31936

American (AMR) AF: 0.00 AC: 0 AN: 42108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25010

East Asian (EAS) AF: 0.00 AC: 0 AN: 37076

South Asian (SAS) AF: 0.0000896 AC: 7 AN: 78152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5582

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085482

Other (OTH) AF: 0.0000173 AC: 1 AN: 57854

GnomAD4 genome Cov.: 30

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	0.092
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-0.86
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.074
Sift	Benign	0.19	T
Sift4G	Benign	0.10	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.22		Gain of glycosylation at A92 (P = 0.0199)
MVP		0.13
MPC		0.16
ClinPred		0.11	T
GERP RS		-2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.64
Mutation Taster		=97/3	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1473018571; hg19: chr3-48520626;