chr22-40827202-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003932.5(ST13):c.875A>G(p.Asn292Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,613,462 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00093 ( 27 hom. )

Consequence

ST13
NM_003932.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.483

Publications

1 publications found

Variant links:

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]

ST13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031644702).

BP6

Variant 22-40827202-T-C is Benign according to our data. Variant chr22-40827202-T-C is described in ClinVar as Benign. ClinVar VariationId is 714908.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00884 (1346/152244) while in subpopulation AFR AF = 0.0307 (1274/41532). AF 95% confidence interval is 0.0293. There are 18 homozygotes in GnomAd4. There are 651 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

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.875A>G	p.Asn292Ser	missense	Exon 11 of 12	NP_003923.2
	ST13	NM_001278589.2		c.845A>G	p.Asn282Ser	missense	Exon 11 of 12	NP_001265518.1	B4E0U6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ST13	ENST00000216218.8	TSL:1 MANE Select	c.875A>G	p.Asn292Ser	missense	Exon 11 of 12	ENSP00000216218.3	P50502
ST13	ENST00000893870.1		c.992A>G	p.Asn331Ser	missense	Exon 12 of 13	ENSP00000563929.1
ST13	ENST00000893867.1		c.950A>G	p.Asn317Ser	missense	Exon 12 of 13	ENSP00000563926.1

Frequencies

GnomAD3 genomes

AF:

0.00881

AC:

1340

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00238

AC:

595

AN:

249526

AF XY:

0.00179

show subpopulations

Gnomad AFR exome

AF:

0.0323

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.000657

GnomAD4 exome

AF:

0.000932

AC:

1362

AN:

1461218

Hom.:

Cov.:

AF XY:

0.000827

AC XY:

601

AN XY:

726924

show subpopulations

African (AFR)

AF:

0.0309

AC:

1034

AN:

33462

American (AMR)

AF:

0.00157

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00109

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53080

Middle Eastern (MID)

AF:

0.00107

AC:

AN:

5592

European-Non Finnish (NFE)

AF:

0.0000270

AC:

AN:

1111954

Other (OTH)

AF:

0.00212

AC:

128

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

142

213

284

355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00884

AC:

1346

AN:

152244

Hom.:

Cov.:

AF XY:

0.00875

AC XY:

651

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0307

AC:

1274

AN:

41532

American (AMR)

AF:

0.00340

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68018

Other (OTH)

AF:

0.00332

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

151

227

302

378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000747

Hom.:

Bravo

AF:

0.00975

ESP6500AA

AF:

0.0322

AC:

142

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00296

AC:

359

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

2.4

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.063

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.90

PhyloP100

0.48

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.33

REVEL

Benign

0.12

Sift

Benign

0.86

Sift4G

Benign

0.079

Polyphen

0.013

Vest4

0.11

MVP

0.35

MPC

0.28

ClinPred

0.0012

GERP RS

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.44

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over