Variant 6-125889687-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181782.5(NCOA7):c.1633T>A(p.Leu545Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

NCOA7
NM_181782.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0390

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026132822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA7	NM_181782.5 linkuse as main transcript	c.1633T>A	p.Leu545Ile	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.1633T>A	p.Leu545Ile	missense_variant	9/16	1	NM_181782.5	Q8NI08-1
NCOA7	ENST00000368357.7 linkuse as main transcript	c.1633T>A	p.Leu545Ile	missense_variant	10/17	1		Q8NI08-1
NCOA7	ENST00000229634.13 linkuse as main transcript	c.1288T>A	p.Leu430Ile	missense_variant	8/15	2		Q8NI08-7

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250240

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.0000631

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000123

AC:

180

AN:

1461790

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000152

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000559

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Sep 22, 2023

The c.1633T>A (p.L545I) alteration is located in exon 11 (coding exon 8) of the NCOA7 gene. This alteration results from a T to A substitution at nucleotide position 1633, causing the leucine (L) at amino acid position 545 to be replaced by an isoleucine (I). 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

0.063

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.60

Cadd

Benign

6.6

Dann

Benign

0.92

DEOGEN2

Benign

0.0039

T;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.37

M_CAP

Benign

0.0030

MetaRNN

Benign

0.026

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

L;L;.

MutationTaster

Benign

0.75

D;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

0.040

N;N;N

REVEL

Benign

0.041

Sift

Benign

0.47

T;T;T

Sift4G

Benign

0.48

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.084

MVP

0.082

MPC

0.096

ClinPred

0.027

GERP RS

1.2

Varity_R

0.025

gMVP

0.081

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