Genetic Variant NCOA7:p.Ser295Ser (chr6-125888939-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_181782.5(NCOA7):c.885T>C(p.Ser295Ser) variant causes a splice region, synonymous 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NCOA7
NM_181782.5 splice_region, synonymous

Scores

Splicing: ADA: 0.3778

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.71

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 6-125888939-T-C is Benign according to our data. Variant chr6-125888939-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3918115.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.71 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA7	NM_181782.5 link	c.885T>C	p.Ser295Ser	splice_region_variant, synonymous_variant	Exon 9 of 16	ENST00000392477.7	NP_861447.3	Q8NI08-1Q8N3C8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NCOA7	ENST00000392477.7 link	c.885T>C	p.Ser295Ser	splice_region_variant, synonymous_variant	Exon 9 of 16	1	NM_181782.5	ENSP00000376269.2	Q8NI08-1
NCOA7	ENST00000368357.7 link	c.885T>C	p.Ser295Ser	splice_region_variant, synonymous_variant	Exon 10 of 17	1		ENSP00000357341.3	Q8NI08-1
NCOA7	ENST00000229634.13 link	c.573-33T>C		intron_variant	Intron 7 of 14	2		ENSP00000229634.9	Q8NI08-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

235360

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1435652

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711478

African (AFR)

AF:

0.00

AC:

AN:

32270

American (AMR)

AF:

0.00

AC:

AN:

40542

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24980

East Asian (EAS)

AF:

0.00

AC:

AN:

39290

South Asian (SAS)

AF:

0.00

AC:

AN:

82738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52740

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098412

Other (OTH)

AF:

0.00

AC:

AN:

59068

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 04, 2025

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.38

dbscSNV1_RF

Benign

0.28

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over