Variant 6-125889135-A-G 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.1081A>G(p.Lys361Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: not found (cov: 33)

Consequence

NCOA7
NM_181782.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.347

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:

NCOA7 (HGNC:):

NCOA7 links:

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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=0.043864816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOA7	NM_181782.5 linkuse as main transcript	c.1081A>G	p.Lys361Glu	missense_variant	9/16	ENST00000392477.7	NP_861447.3	Q8NI08-1Q8N3C8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NCOA7	ENST00000392477.7 linkuse as main transcript	c.1081A>G	p.Lys361Glu	missense_variant	9/16	1	NM_181782.5	ENSP00000376269.2	Q8NI08-1
NCOA7	ENST00000368357.7 linkuse as main transcript	c.1081A>G	p.Lys361Glu	missense_variant	10/17	1		ENSP00000357341.3	Q8NI08-1
NCOA7	ENST00000229634.13 linkuse as main transcript	c.736A>G	p.Lys246Glu	missense_variant	8/15	2		ENSP00000229634.9	Q8NI08-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250594

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135434

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

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 01, 2024

The c.1081A>G (p.K361E) 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 1081, causing the lysine (K) at amino acid position 361 to be replaced by a glutamic acid (E). 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

0.071

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.1

DANN

Benign

0.68

DEOGEN2

Benign

0.0050

T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.59

.;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.044

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.81

L;L;.

PrimateAI

Benign

0.27

PROVEAN

Benign

0.85

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.77

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.097

MutPred

0.21

Loss of ubiquitination at K361 (P = 0.002);Loss of ubiquitination at K361 (P = 0.002);.;

MVP

0.043

MPC

0.13

ClinPred

0.037

GERP RS

-0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.036

gMVP

0.15

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