rs3829037

Variant names:

Variant summary

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

The NM_014751.6(MTSS1):c.2173A>G(p.Thr725Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,730 control chromosomes in the GnomAD database, including 39,142 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.19 ( 3037 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36105 hom. )

Consequence

MTSS1
NM_014751.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.218

Publications

35 publications found

Variant links:

Genes affected

MTSS1 (HGNC:20443): (MTSS I-BAR domain containing 1) Enables actin monomer binding activity; identical protein binding activity; and signaling receptor binding activity. Predicted to be involved in cellular response to fluid shear stress; negative regulation of epithelial cell proliferation; and urogenital system development. Predicted to act upstream of or within several processes, including actin filament polymerization; adherens junction maintenance; and magnesium ion homeostasis. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

MTSS1 links:

NDUFB9 (HGNC:7704): (NADH:ubiquinone oxidoreductase subunit B9) The protein encoded by this gene is a subunit of the mitochondrial oxidative phosphorylation complex I (nicotinamide adenine dinucleotide: ubiquinone oxidoreductase). Complex I is localized to the inner mitochondrial membrane and functions to dehydrogenate nicotinamide adenine dinucleotide and to shuttle electrons to coenzyme Q. Complex I deficiency is the most common defect found in oxidative phosphorylation disorders and results in a range of conditions, including lethal neonatal disease, hypertrophic cardiomyopathy, liver disease, and adult-onset neurodegenerative disorders. Pseudogenes of this gene are found on chromosomes five, seven and eight. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

NDUFB9 Gene-Disease associations (from GenCC):

mitochondrial complex I deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
mitochondrial complex I deficiency, nuclear type 24
Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

NDUFB9 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=0.0028086603).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTSS1	NM_014751.6 link	c.2173A>G	p.Thr725Ala	missense_variant	Exon 14 of 14	ENST00000518547.6	NP_055566.3	O43312-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTSS1	ENST00000518547.6 link	c.2173A>G	p.Thr725Ala	missense_variant	Exon 14 of 14	1	NM_014751.6	ENSP00000429064.1		O43312-1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29192

AN:

151762

Hom.:

3035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.132

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.161

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.196

AC:

49237

AN:

251494

AF XY:

0.199

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.0895

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.219

AC:

319847

AN:

1461850

Hom.:

36105

Cov.:

AF XY:

0.217

AC XY:

157997

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.150

AC:

5030

AN:

33480

American (AMR)

AF:

0.0939

AC:

4199

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

5359

AN:

26136

East Asian (EAS)

AF:

0.199

AC:

7913

AN:

39700

South Asian (SAS)

AF:

0.164

AC:

14189

AN:

86258

European-Finnish (FIN)

AF:

0.303

AC:

16194

AN:

53420

Middle Eastern (MID)

AF:

0.249

AC:

1434

AN:

5768

European-Non Finnish (NFE)

AF:

0.227

AC:

252795

AN:

1111972

Other (OTH)

AF:

0.211

AC:

12734

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

16575

33150

49726

66301

82876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8684

17368

26052

34736

43420

<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:

0.192

AC:

29201

AN:

151880

Hom.:

3037

Cov.:

AF XY:

0.196

AC XY:

14563

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.147

AC:

6093

AN:

41422

American (AMR)

AF:

0.126

AC:

1921

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

719

AN:

3464

East Asian (EAS)

AF:

0.171

AC:

884

AN:

5162

South Asian (SAS)

AF:

0.161

AC:

778

AN:

4820

European-Finnish (FIN)

AF:

0.308

AC:

3233

AN:

10504

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

14998

AN:

67958

Other (OTH)

AF:

0.184

AC:

388

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1210

2421

3631

4842

6052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.209

Hom.:

14818

Bravo

AF:

0.179

TwinsUK

AF:

0.224

AC:

829

ALSPAC

AF:

0.223

AC:

859

ESP6500AA

AF:

0.149

AC:

657

ESP6500EA

AF:

0.216

AC:

1858

ExAC

AF:

0.199

AC:

24215

Asia WGS

AF:

0.153

AC:

530

AN:

3478

EpiCase

AF:

0.217

EpiControl

AF:

0.219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.0

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.18

.;T;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.68

T;T;T;T;T

MetaRNN

Benign

0.0028

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.32

.;N;.;.;.

PhyloP100

0.22

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.56

N;N;N;N;N

REVEL

Benign

0.097

Sift

Benign

0.80

T;T;T;T;T

Sift4G

Benign

0.93

T;T;T;T;T

Polyphen

0.0

B;B;.;B;B

Vest4

0.025

MPC

0.35

ClinPred

0.0018

GERP RS

-4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.13

Mutation Taster

=96/4

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over