6-125889600-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181782.5(NCOA7):c.1546G>A(p.Asp516Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,492 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NCOA7 NM_181782.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.99

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18767706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOA7	NM_181782.5	c.1546G>A	p.Asp516Asn	missense_variant	9/16	ENST00000392477.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOA7	ENST00000392477.7	c.1546G>A	p.Asp516Asn	missense_variant	9/16	1	NM_181782.5
NCOA7	ENST00000368357.7	c.1546G>A	p.Asp516Asn	missense_variant	10/17	1
NCOA7	ENST00000229634.13	c.1201G>A	p.Asp401Asn	missense_variant	8/15	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461492 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 727056

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2023

The c.1546G>A (p.D516N) alteration is located in exon 11 (coding exon 8) of the NCOA7 gene. This alteration results from a G to A substitution at nucleotide position 1546, causing the aspartic acid (D) at amino acid position 516 to be replaced by an asparagine (N). 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	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.013	T;T;.
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;.
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.76	N;N;N
REVEL	Benign	0.13
Sift	Uncertain	0.0010	D;D;D
Sift4G	Benign	0.39	T;T;T
Polyphen		0.80	P;P;.
Vest4		0.16
MutPred		0.26		Gain of methylation at K519 (P = 0.0801);Gain of methylation at K519 (P = 0.0801);.;
MVP		0.31
MPC		0.24
ClinPred		0.89	D
GERP RS		5.8
Varity_R		0.13
gMVP		0.31

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

Other links and lift over

dbSNP: rs1784485965; hg19: chr6-126210746;