6-125881112-A-T

Variant names:

• chr6-125881112-A-T
• rs771850255
• NM_181782.5:c.482A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181782.5(NCOA7):​c.482A>T​(p.Asn161Ile) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N161S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NCOA7 NM_181782.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16044736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA7	NM_181782.5	c.482A>T	p.Asn161Ile	missense_variant	Exon 6 of 16	ENST00000392477.7	NP_861447.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7	c.482A>T	p.Asn161Ile	missense_variant	Exon 6 of 16	1	NM_181782.5	ENSP00000376269.2
NCOA7	ENST00000368357.7	c.482A>T	p.Asn161Ile	missense_variant	Exon 7 of 17	1		ENSP00000357341.3
NCOA7	ENST00000229634.13	c.170A>T	p.Asn57Ile	missense_variant	Exon 5 of 15	2		ENSP00000229634.9
NCOA7	ENST00000417494.5	c.482A>T	p.Asn161Ile	missense_variant	Exon 6 of 6	2		ENSP00000406363.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;T;.
Eigen	Benign	0.057
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.76	.;T;T;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;.;.
PhyloP100		1.1
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.053
Sift	Uncertain	0.0050	D;D;T;D
Sift4G	Uncertain	0.011	D;D;D;D
Polyphen		0.76	P;P;.;.
Vest4		0.32
MutPred		0.32		Loss of catalytic residue at N161 (P = 0.0076);Loss of catalytic residue at N161 (P = 0.0076);Loss of catalytic residue at N161 (P = 0.0076);.;
MVP		0.14
MPC		0.21
ClinPred		0.94	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.21
gMVP		0.37
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs771850255; hg19: chr6-126202258;