rs62063857

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001007532.3(STH):c.20A>G(p.Gln7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,188 control chromosomes in the GnomAD database, including 32,786 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2149 hom., cov: 32)

Exomes 𝑓: 0.19 ( 30637 hom. )

Consequence

STH
NM_001007532.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

51 publications found

Variant links:

Genes affected

STH (HGNC:18839): (saitohin) Involved in positive regulation of mRNA splicing, via spliceosome. Located in nucleus and perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

STH links:

MAPT (HGNC:6893): (microtubule associated protein tau) This gene encodes the microtubule-associated protein tau (MAPT) whose transcript undergoes complex, regulated alternative splicing, giving rise to several mRNA species. MAPT transcripts are differentially expressed in the nervous system, depending on stage of neuronal maturation and neuron type. MAPT gene mutations have been associated with several neurodegenerative disorders such as Alzheimer's disease, Pick's disease, frontotemporal dementia, cortico-basal degeneration and progressive supranuclear palsy. [provided by RefSeq, Jul 2008]

MAPT Gene-Disease associations (from GenCC):

Pick disease
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
semantic dementia
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
supranuclear palsy, progressive, 1
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
late-onset Parkinson disease
Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
progressive supranuclear palsy-parkinsonism syndrome
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp

MAPT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0050816536).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STH	NM_001007532.3 link	c.20A>G	p.Gln7Arg	missense_variant	Exon 1 of 1	ENST00000537309.1	NP_001007533.1
MAPT	NM_001377265.1 link	c.1998+2635A>G		intron_variant	Intron 9 of 12	ENST00000262410.10	NP_001364194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STH	ENST00000537309.1 link	c.20A>G	p.Gln7Arg	missense_variant	Exon 1 of 1	6	NM_001007532.3	ENSP00000443168.1
MAPT	ENST00000262410.10 link	c.1998+2635A>G		intron_variant	Intron 9 of 12	1	NM_001377265.1	ENSP00000262410.6

Frequencies

GnomAD3 genomes

AF:

0.145

AC:

22079

AN:

151952

Hom.:

2151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0491

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.176

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.0742

Gnomad FIN

AF:

0.0652

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.145

AC:

35663

AN:

246198

AF XY:

0.148

show subpopulations

Gnomad AFR exome

AF:

0.0472

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.000668

Gnomad FIN exome

AF:

0.0678

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.173

GnomAD4 exome

AF:

0.194

AC:

282835

AN:

1461114

Hom.:

30637

Cov.:

AF XY:

0.191

AC XY:

138909

AN XY:

726802

show subpopulations

African (AFR)

AF:

0.0428

AC:

1433

AN:

33472

American (AMR)

AF:

0.125

AC:

5610

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

6695

AN:

26128

East Asian (EAS)

AF:

0.000882

AC:

AN:

39696

South Asian (SAS)

AF:

0.0796

AC:

6863

AN:

86212

European-Finnish (FIN)

AF:

0.0724

AC:

3865

AN:

53392

Middle Eastern (MID)

AF:

0.200

AC:

1103

AN:

5514

European-Non Finnish (NFE)

AF:

0.222

AC:

246540

AN:

1111652

Other (OTH)

AF:

0.177

AC:

10691

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

13172

26344

39516

52688

65860

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8232

16464

24696

32928

41160

<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:

0.145

AC:

22069

AN:

152074

Hom.:

2149

Cov.:

AF XY:

0.136

AC XY:

10126

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0490

AC:

2035

AN:

41496

American (AMR)

AF:

0.176

AC:

2685

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

835

AN:

3472

East Asian (EAS)

AF:

0.00155

AC:

AN:

5158

South Asian (SAS)

AF:

0.0743

AC:

358

AN:

4818

European-Finnish (FIN)

AF:

0.0652

AC:

691

AN:

10602

Middle Eastern (MID)

AF:

0.216

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.217

AC:

14755

AN:

67940

Other (OTH)

AF:

0.183

AC:

386

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

945

1889

2834

3778

4723

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.195

Hom.:

8256

Bravo

AF:

0.150

TwinsUK

AF:

0.233

AC:

864

ALSPAC

AF:

0.241

AC:

930

ESP6500AA

AF:

0.0474

AC:

187

ESP6500EA

AF:

0.220

AC:

1836

ExAC

AF:

0.145

AC:

17535

Asia WGS

AF:

0.0320

AC:

112

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0060

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.0013

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00014

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-2.1

PrimateAI

Benign

0.29

PROVEAN

Benign

3.0

REVEL

Benign

0.081

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.010

MPC

0.0097

ClinPred

0.00065

GERP RS

-0.94

PromoterAI

0.021

Neutral

(source)

Varity_R

0.031

gMVP

0.0019

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over