22-40844874-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3360868).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ST13	NM_003932.5	c.280G>A	p.Asp94Asn	missense_variant	Exon 4 of 12	ENST00000216218.8	NP_003923.2
ST13	NM_001278589.2	c.250G>A	p.Asp84Asn	missense_variant	Exon 4 of 12		NP_001265518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ST13	ENST00000216218.8	c.280G>A	p.Asp94Asn	missense_variant	Exon 4 of 12	1	NM_003932.5	ENSP00000216218.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.280G>A (p.D94N) alteration is located in exon 4 (coding exon 4) of the ST13 gene. This alteration results from a G to A substitution at nucleotide position 280, causing the aspartic acid (D) at amino acid position 94 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Uncertain	-0.22	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.2	D;.;D
REVEL	Benign	0.25
Sift	Uncertain	0.0050	D;.;D
Sift4G	Benign	0.095	T;D;.
Polyphen		1.0	D;.;.
Vest4		0.50
MutPred		0.21		Gain of glycosylation at T93 (P = 0.1144);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-41240878;