NM_016479.6:c.403C>A

Variant names:

• chr3-48469755-G-T
• NM_016479.6:c.403C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016479.6(SHISA5):​c.403C>A​(p.Leu135Ile) 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. 14/22 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)
• Consequence: SHISA5 NM_016479.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.629
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28872046).

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.403C>A	p.Leu135Ile	missense	Exon 4 of 6	NP_057563.3
	SHISA5	NM_001272065.3		c.382C>A	p.Leu128Ile	missense	Exon 4 of 6	NP_001258994.1	Q8N114-5
	SHISA5	NM_001272066.2		c.310C>A	p.Leu104Ile	missense	Exon 4 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.403C>A	p.Leu135Ile	missense	Exon 4 of 6	ENSP00000296444.2	Q8N114-1
	SHISA5	ENST00000426002.5	TSL:1	c.94C>A	p.Leu32Ile	missense	Exon 2 of 4	ENSP00000390388.1	Q8N114-3
	SHISA5	ENST00000460758.1	TSL:1	n.207C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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	0.20
BayesDel_addAF	Benign	-0.033	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.63
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.15
Sift	Benign	0.079	T
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.26		Loss of helix (P = 0.0558)
MVP		0.31
MPC		0.63
ClinPred		0.89	D
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.083
gMVP		0.33
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

hg19: chr3-48511154;