NM_003932.5:c.171A>T

Variant names:

• chr22-40848367-T-A
• rs934552778
• NM_003932.5:c.171A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003932.5(ST13):​c.171A>T​(p.Glu57Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,608,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: ST13 NM_003932.5 missense, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.203
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09389594).

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.171A>T	p.Glu57Asp	missense splice_region	Exon 3 of 12	NP_003923.2
	ST13	NM_001278589.2		c.169-28A>T		intron	N/A	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.171A>T	p.Glu57Asp	missense splice_region	Exon 3 of 12	ENSP00000216218.3	P50502
	ST13	ENST00000893870.1		c.171A>T	p.Glu57Asp	missense splice_region	Exon 3 of 13	ENSP00000563929.1
	ST13	ENST00000893867.1		c.171A>T	p.Glu57Asp	missense splice_region	Exon 3 of 13	ENSP00000563926.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152248 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1456634 Hom.: 0 Cov.: 29 AF XY: 0.0000124 AC XY: 9 AN XY: 724954

African (AFR) AF: 0.0000299 AC: 1 AN: 33392

American (AMR) AF: 0.0000671 AC: 3 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00000812 AC: 9 AN: 1108358

Other (OTH) AF: 0.0000830 AC: 5 AN: 60208

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74378

African (AFR) AF: 0.0000241 AC: 1 AN: 41470

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

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	0.089
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.63	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.094	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.20
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.065
Sift	Benign	0.31	T
Sift4G	Benign	0.25	T
Polyphen		0.067	B
Vest4		0.31
MutPred		0.22		Loss of methylation at K59 (P = 0.1048)
MVP		0.61
MPC		0.33
ClinPred		0.33	T
GERP RS		0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.099
gMVP		0.052
Mutation Taster		=90/10	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

dbSNP: rs934552778; hg19: chr22-41244371;