NM_003932.5:c.280G>A

Variant names:

• chr22-40844874-C-T
• NM_003932.5:c.280G>A

Variant summary

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

The NM_003932.5(ST13):​c.280G>A​(p.Asp94Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D94E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ST13 NM_003932.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25
• Publications: 0 publications found

Genes affected

ST13 (HGNC:11343): (ST13 Hsp70 interacting protein) The protein encoded by this gene is an adaptor protein that mediates the association of the heat shock proteins HSP70 and HSP90. This protein has been shown to be involved in the assembly process of glucocorticoid receptor, which requires the assistance of multiple molecular chaperones. The expression of this gene is reported to be downregulated in colorectal carcinoma tissue suggesting that it is a candidate tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]

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=0.3360868).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003932.5. 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
	ST13	NM_003932.5	MANE Select	c.280G>A	p.Asp94Asn	missense	Exon 4 of 12	NP_003923.2
	ST13	NM_001278589.2		c.250G>A	p.Asp84Asn	missense	Exon 4 of 12	NP_001265518.1	B4E0U6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ST13	ENST00000216218.8	TSL:1 MANE Select	c.280G>A	p.Asp94Asn	missense	Exon 4 of 12	ENSP00000216218.3	P50502
	ST13	ENST00000893870.1		c.280G>A	p.Asp94Asn	missense	Exon 4 of 13	ENSP00000563929.1
	ST13	ENST00000893867.1		c.355G>A	p.Asp119Asn	missense	Exon 5 of 13	ENSP00000563926.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.32
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	-0.22	T
PhyloP100		5.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.095	T
Polyphen		1.0	D
Vest4		0.50
MutPred		0.21		Gain of glycosylation at T93 (P = 0.1144)
MVP		0.68
MPC		0.37
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.31
gMVP		0.38
Mutation Taster		=61/39	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: chr22-41240878;