Variant 6-125889595-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181782.5(NCOA7):c.1541A>G(p.His514Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

NCOA7
NM_181782.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

NCOA7 (HGNC:21081): (nuclear receptor coactivator 7) Enables nuclear receptor binding activity and nuclear receptor coactivator activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NCOA7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07792178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA7	NM_181782.5 linkuse as main transcript	c.1541A>G	p.His514Arg	missense_variant	9/16	ENST00000392477.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
NCOA7	ENST00000392477.7 linkuse as main transcript	c.1541A>G	p.His514Arg	missense_variant	9/16	1	NM_181782.5	Q8NI08-1
NCOA7	ENST00000368357.7 linkuse as main transcript	c.1541A>G	p.His514Arg	missense_variant	10/17	1		Q8NI08-1
NCOA7	ENST00000229634.13 linkuse as main transcript	c.1196A>G	p.His399Arg	missense_variant	8/15	2		Q8NI08-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000400

AC:

AN:

249800

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

135314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461602

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2022

The c.1541A>G (p.H514R) alteration is located in exon 11 (coding exon 8) of the NCOA7 gene. This alteration results from a A to G substitution at nucleotide position 1541, causing the histidine (H) at amino acid position 514 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.28

Cadd

Benign

Dann

Benign

0.81

DEOGEN2

Benign

0.0097

T;T;.

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.011

FATHMM_MKL

Benign

0.58

M_CAP

Benign

0.0046

MetaRNN

Benign

0.078

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;.

MutationTaster

Benign

0.83

N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.65

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.076

T;T;T

Sift4G

Benign

0.53

T;T;T

Polyphen

0.29

B;B;.

Vest4

0.18

MutPred

0.18

Gain of disorder (P = 0.0915);Gain of disorder (P = 0.0915);.;

MVP

0.19

MPC

0.14

ClinPred

0.061

GERP RS

4.6

Varity_R

0.079

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over