chr6-125885315-C-G

Variant names:

• chr6-125885315-C-G
• rs1784164878
• NM_181782.5:c.856C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_181782.5(NCOA7):​c.856C>G​(p.His286Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCOA7 NM_181782.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.00
• Publications: 0 publications found

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]

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39933977).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA7	NM_181782.5	c.856C>G	p.His286Asp	missense_variant	Exon 8 of 16	ENST00000392477.7	NP_861447.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7	c.856C>G	p.His286Asp	missense_variant	Exon 8 of 16	1	NM_181782.5	ENSP00000376269.2
NCOA7	ENST00000368357.7	c.856C>G	p.His286Asp	missense_variant	Exon 9 of 17	1		ENSP00000357341.3
NCOA7	ENST00000229634.13	c.544C>G	p.His182Asp	missense_variant	Exon 7 of 15	2		ENSP00000229634.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.856C>G (p.H286D) alteration is located in exon 10 (coding exon 7) of the NCOA7 gene. This alteration results from a C to G substitution at nucleotide position 856, causing the histidine (H) at amino acid position 286 to be replaced by an aspartic acid (D). 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	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T;T;.
Eigen	Benign	-0.056
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	.;T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;.
PhyloP100		6.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.44	N;N;N
REVEL	Benign	0.15
Sift	Benign	0.19	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.52	P;P;.
Vest4		0.73
MutPred		0.31		Gain of ubiquitination at K288 (P = 0.0662);Gain of ubiquitination at K288 (P = 0.0662);.;
MVP		0.11
MPC		0.30
ClinPred		0.51	D
GERP RS		5.6
Varity_R		0.19
gMVP		0.83
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs1784164878; hg19: chr6-126206461;