Genetic Variant NCOA7:p.Met105Val (chr6-125874930-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PVS1_Supporting

The NM_001199621.2(NCOA7):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.000288 in 1,613,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

NCOA7
NM_001199621.2 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.69

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:

RN7SKP56 (HGNC:45780): (RN7SK pseudogene 56)

RN7SKP56 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 10 codons. Genomic position: 125874957. Lost 0.011 part of the original CDS.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA7	NM_181782.5 link	c.313A>G	p.Met105Val	missense_variant	Exon 4 of 16	ENST00000392477.7	NP_861447.3	Q8NI08-1Q8N3C8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7 link	c.313A>G	p.Met105Val	missense_variant	Exon 4 of 16	1	NM_181782.5	ENSP00000376269.2		Q8NI08-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000338

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000267

AC:

AN:

251176

AF XY:

0.000214

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000414

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000301

AC:

440

AN:

1461422

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33470

American (AMR)

AF:

0.000380

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000361

AC:

401

AN:

1111652

Other (OTH)

AF:

0.000298

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000164

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41564

American (AMR)

AF:

0.0000653

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.000181

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 01, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.313A>G (p.M105V) alteration is located in exon 6 (coding exon 3) of the NCOA7 gene. This alteration results from a A to G substitution at nucleotide position 313, causing the methionine (M) at amino acid position 105 to be replaced by a valine (V). 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

0.25

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T;T;.;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

.;D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.15

T;T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

2.0

M;M;.;.;.

PhyloP100

6.7

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.4

N;N;D;N;D

REVEL

Benign

0.21

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.010

D;D;D;D;D

Polyphen

0.98

D;D;.;.;.

Vest4

0.59

MVP

0.11

MPC

0.47

ClinPred

0.11

GERP RS

5.3

Varity_R

0.58

gMVP

0.42

Mutation Taster

=14/186

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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6-125874930-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over