Genetic Variant NCOA5:p.Thr443Thr (chr20-46062711-T-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020967.3(NCOA5):c.1329A>C(p.Thr443Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,613,796 control chromosomes in the GnomAD database, including 96,895 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.32 ( 8358 hom., cov: 32)

Exomes 𝑓: 0.34 ( 88537 hom. )

Consequence

NCOA5
NM_020967.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.82

Publications

29 publications found

Variant links:

Genes affected

NCOA5 (HGNC:15909): (nuclear receptor coactivator 5) This gene encodes a coregulator for the alpha and beta estrogen receptors and the orphan nuclear receptor NR1D2. The protein localizes to the nucleus, and is thought to have both coactivator and corepressor functions. Its interaction with nuclear receptors is independent of the AF2 domain on the receptors, which is known to regulate interaction with other coreceptors. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2017]

NCOA5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP7

Synonymous conserved (PhyloP=-2.82 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA5	NM_020967.3 link	c.1329A>C	p.Thr443Thr	synonymous_variant	Exon 8 of 8	ENST00000290231.11	NP_066018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA5	ENST00000290231.11 link	c.1329A>C	p.Thr443Thr	synonymous_variant	Exon 8 of 8	1	NM_020967.3	ENSP00000290231.6		Q9HCD5

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49095

AN:

151856

Hom.:

8349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.335

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.355

GnomAD2 exomes

AF:

0.375

AC:

94263

AN:

251378

AF XY:

0.370

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.529

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.576

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.336

Gnomad OTH exome

AF:

0.367

GnomAD4 exome

AF:

0.342

AC:

499902

AN:

1461822

Hom.:

88537

Cov.:

AF XY:

0.343

AC XY:

249172

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.255

AC:

8524

AN:

33480

American (AMR)

AF:

0.514

AC:

22978

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

8661

AN:

26132

East Asian (EAS)

AF:

0.593

AC:

23527

AN:

39698

South Asian (SAS)

AF:

0.377

AC:

32482

AN:

86256

European-Finnish (FIN)

AF:

0.281

AC:

15027

AN:

53418

Middle Eastern (MID)

AF:

0.350

AC:

2016

AN:

5766

European-Non Finnish (NFE)

AF:

0.329

AC:

366087

AN:

1111958

Other (OTH)

AF:

0.341

AC:

20600

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

21910

43820

65730

87640

109550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11980

23960

35940

47920

59900

<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:

0.323

AC:

49118

AN:

151974

Hom.:

8358

Cov.:

AF XY:

0.323

AC XY:

24028

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.256

AC:

10619

AN:

41446

American (AMR)

AF:

0.428

AC:

6532

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.335

AC:

1164

AN:

3470

East Asian (EAS)

AF:

0.569

AC:

2934

AN:

5154

South Asian (SAS)

AF:

0.375

AC:

1806

AN:

4822

European-Finnish (FIN)

AF:

0.265

AC:

2798

AN:

10574

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.326

AC:

22112

AN:

67932

Other (OTH)

AF:

0.358

AC:

751

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1681

3362

5042

6723

8404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

488

976

1464

1952

2440

<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:

0.329

Hom.:

11394

Bravo

AF:

0.338

Asia WGS

AF:

0.492

AC:

1712

AN:

3478

EpiCase

AF:

0.335

EpiControl

AF:

0.341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.34

(source)

DANN

Benign

0.61

PhyloP100

-2.8

Mutation Taster

=98/2

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