Genetic Variant NM_001350921.2:c.1075G>A (chr10-126504416-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001350921.2(C10orf90):c.1075G>A(p.Asp359Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 1,613,930 control chromosomes in the GnomAD database, including 93,769 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.40 ( 13894 hom., cov: 32)

Exomes 𝑓: 0.32 ( 79875 hom. )

Consequence

C10orf90
NM_001350921.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.60

Publications

29 publications found

Variant links:

Genes affected

C10orf90 (HGNC:26563): (chromosome 10 open reading frame 90) Predicted to enable histone deacetylase binding activity; microtubule binding activity; and ubiquitin protein ligase activity. Predicted to be involved in several processes, including protein stabilization; regulation of cell cycle process; and response to ionizing radiation. Located in several cellular components, including cytoskeleton; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

C10orf90 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=6.0354714E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C10orf90	NM_001350921.2 link	c.1075G>A	p.Asp359Asn	missense_variant	Exon 4 of 10	ENST00000488181.3	NP_001337850.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C10orf90	ENST00000488181.3 link	c.1075G>A	p.Asp359Asn	missense_variant	Exon 4 of 10	2	NM_001350921.2	ENSP00000474558.3		S4R3N7

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61014

AN:

151928

Hom.:

13856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.401

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.503

Gnomad SAS

AF:

0.465

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.377

GnomAD2 exomes

AF:

0.372

AC:

93548

AN:

251316

AF XY:

0.368

show subpopulations

Gnomad AFR exome

AF:

0.621

Gnomad AMR exome

AF:

0.438

Gnomad ASJ exome

AF:

0.366

Gnomad EAS exome

AF:

0.510

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.340

GnomAD4 exome

AF:

0.321

AC:

469720

AN:

1461884

Hom.:

79875

Cov.:

AF XY:

0.324

AC XY:

235296

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.632

AC:

21168

AN:

33480

American (AMR)

AF:

0.434

AC:

19391

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

9526

AN:

26136

East Asian (EAS)

AF:

0.487

AC:

19349

AN:

39700

South Asian (SAS)

AF:

0.451

AC:

38944

AN:

86258

European-Finnish (FIN)

AF:

0.270

AC:

14416

AN:

53420

Middle Eastern (MID)

AF:

0.350

AC:

2017

AN:

5768

European-Non Finnish (NFE)

AF:

0.291

AC:

323924

AN:

1112004

Other (OTH)

AF:

0.347

AC:

20985

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

22025

44050

66076

88101

110126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11146

22292

33438

44584

55730

<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:

0.402

AC:

61113

AN:

152046

Hom.:

13894

Cov.:

AF XY:

0.403

AC XY:

29979

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.612

AC:

25372

AN:

41458

American (AMR)

AF:

0.400

AC:

6122

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.357

AC:

1237

AN:

3466

East Asian (EAS)

AF:

0.503

AC:

2590

AN:

5150

South Asian (SAS)

AF:

0.465

AC:

2239

AN:

4816

European-Finnish (FIN)

AF:

0.259

AC:

2746

AN:

10582

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.290

AC:

19742

AN:

67972

Other (OTH)

AF:

0.381

AC:

804

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1699

3398

5098

6797

8496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

560

1120

1680

2240

2800

<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:

0.339

Hom.:

21039

Bravo

AF:

0.423

TwinsUK

AF:

0.295

AC:

1095

ALSPAC

AF:

0.298

AC:

1147

ESP6500AA

AF:

0.595

AC:

2620

ESP6500EA

AF:

0.302

AC:

2596

ExAC

AF:

0.374

AC:

45369

Asia WGS

AF:

0.494

AC:

1716

AN:

3478

EpiCase

AF:

0.302

EpiControl

AF:

0.296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.6

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.017

T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.20

T;T;T

MetaRNN

Benign

0.0000060

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.1

N;.;.

PhyloP100

1.6

PROVEAN

Benign

1.1

N;N;N

REVEL

Benign

0.065

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.053

MPC

0.074

ClinPred

0.00030

GERP RS

1.6

PromoterAI

0.0048

Neutral

(source)

Varity_R

0.025

gMVP

0.056

Mutation Taster

=100/0

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