6-125882507-G-A

Variant names:

• chr6-125882507-G-A
• rs1783924730
• NM_181782.5:c.655G>A

Variant summary

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

The NM_181782.5(NCOA7):​c.655G>A​(p.Val219Met) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 9.91
• 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=0.34713465).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA7	NM_181782.5	c.655G>A	p.Val219Met	missense_variant	Exon 7 of 16	ENST00000392477.7	NP_861447.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7	c.655G>A	p.Val219Met	missense_variant	Exon 7 of 16	1	NM_181782.5	ENSP00000376269.2
NCOA7	ENST00000368357.7	c.655G>A	p.Val219Met	missense_variant	Exon 8 of 17	1		ENSP00000357341.3
NCOA7	ENST00000229634.13	c.343G>A	p.Val115Met	missense_variant	Exon 6 of 15	2		ENSP00000229634.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.655G>A (p.V219M) alteration is located in exon 9 (coding exon 6) of the NCOA7 gene. This alteration results from a G to A substitution at nucleotide position 655, causing the valine (V) at amino acid position 219 to be replaced by a methionine (M). 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	0.30
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.020	T;T;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	.;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.3	M;M;.
PhyloP100		9.9
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.75	N;N;N
REVEL	Benign	0.24
Sift	Benign	0.041	D;D;T
Sift4G	Benign	0.086	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.51
MutPred		0.23		Gain of loop (P = 0.069);Gain of loop (P = 0.069);.;
MVP		0.18
MPC		0.48
ClinPred		0.84	D
GERP RS		5.6
Varity_R		0.18
gMVP		0.72
Mutation Taster		=60/40	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: rs1783924730; hg19: chr6-126203653;