Genetic Variant NM_014066.4:c.16G>A (chr8-144851323-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_014066.4(COMMD5):c.16G>A(p.Ala6Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,608,156 control chromosomes in the GnomAD database, including 100,539 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.28 ( 7162 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93377 hom. )

Consequence

COMMD5
NM_014066.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.500

Publications

31 publications found

Variant links:

Genes affected

COMMD5 (HGNC:17902): (COMM domain containing 5) Predicted to be involved in proximal tubule morphogenesis. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

COMMD5 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=6.0510635E-4).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COMMD5	NM_014066.4 link	c.16G>A	p.Ala6Thr	missense_variant	Exon 2 of 2	ENST00000305103.4	NP_054785.2	Q9GZQ3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COMMD5	ENST00000305103.4 link	c.16G>A	p.Ala6Thr	missense_variant	Exon 2 of 2	1	NM_014066.4	ENSP00000304544.3		Q9GZQ3

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42835

AN:

151924

Hom.:

7170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.324

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.331

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.365

Gnomad OTH

AF:

0.290

GnomAD2 exomes

AF:

0.327

AC:

81563

AN:

249210

AF XY:

0.345

show subpopulations

Gnomad AFR exome

AF:

0.0942

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.363

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.353

AC:

513617

AN:

1456112

Hom.:

93377

Cov.:

AF XY:

0.358

AC XY:

259024

AN XY:

723384

show subpopulations

African (AFR)

AF:

0.0880

AC:

2935

AN:

33366

American (AMR)

AF:

0.193

AC:

8574

AN:

44448

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

10510

AN:

25916

East Asian (EAS)

AF:

0.269

AC:

10655

AN:

39548

South Asian (SAS)

AF:

0.451

AC:

38779

AN:

85972

European-Finnish (FIN)

AF:

0.332

AC:

17644

AN:

53080

Middle Eastern (MID)

AF:

0.273

AC:

1566

AN:

5742

European-Non Finnish (NFE)

AF:

0.363

AC:

402072

AN:

1107926

Other (OTH)

AF:

0.347

AC:

20882

AN:

60114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

19223

38446

57668

76891

96114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12614

25228

37842

50456

63070

<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:

0.282

AC:

42830

AN:

152044

Hom.:

7162

Cov.:

AF XY:

0.280

AC XY:

20823

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.102

AC:

4250

AN:

41514

American (AMR)

AF:

0.255

AC:

3897

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1417

AN:

3468

East Asian (EAS)

AF:

0.323

AC:

1663

AN:

5152

South Asian (SAS)

AF:

0.453

AC:

2185

AN:

4822

European-Finnish (FIN)

AF:

0.331

AC:

3495

AN:

10548

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.365

AC:

24831

AN:

67944

Other (OTH)

AF:

0.290

AC:

612

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1486

2973

4459

5946

7432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.337

Hom.:

25885

Bravo

AF:

0.266

TwinsUK

AF:

0.371

AC:

1375

ALSPAC

AF:

0.356

AC:

1373

ESP6500AA

AF:

0.101

AC:

447

ESP6500EA

AF:

0.363

AC:

3126

ExAC

AF:

0.328

AC:

39845

Asia WGS

AF:

0.421

AC:

1465

AN:

3478

EpiCase

AF:

0.372

EpiControl

AF:

0.368

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.6

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0031

T;T;T;T;.;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.54

.;T;.;.;.;T

MetaRNN

Benign

0.00061

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

L;L;L;L;.;.

PhyloP100

-0.50

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.33

N;.;N;N;N;N

REVEL

Benign

0.062

Sift

Benign

0.35

T;.;T;T;T;T

Sift4G

Benign

0.12

T;T;T;T;.;T

Polyphen

0.099

B;B;B;B;.;.

Vest4

0.026

MPC

0.13

ClinPred

0.00070

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.016

gMVP

0.30

Mutation Taster

=97/3

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