6-125815383-G-T

Variant names:

• chr6-125815383-G-T
• rs371057703
• NM_181782.5:c.29G>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.29G>T​(p.Arg10Leu) 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. 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. R10Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCOA7 NM_181782.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.03
• 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]

NCOA7-AS1 (HGNC:40954): (NCOA7 antisense RNA 1)

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=0.22187439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA7	NM_181782.5	c.29G>T	p.Arg10Leu	missense_variant	Exon 2 of 16	ENST00000392477.7	NP_861447.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7	c.29G>T	p.Arg10Leu	missense_variant	Exon 2 of 16	1	NM_181782.5	ENSP00000376269.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;T;.;T;.;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.85	.;T;.;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.22	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.;.;.;.
PhyloP100		5.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.73	N;N;D;N;D;N
REVEL	Benign	0.22
Sift	Uncertain	0.0060	D;D;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D
Polyphen		0.99	D;D;.;.;.;.
Vest4		0.67
MutPred		0.14		Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);Loss of MoRF binding (P = 0.0107);
MVP		0.26
MPC		0.15
ClinPred		0.82	D
GERP RS		4.8
PromoterAI		0.063	Neutral
Varity_R		0.18
gMVP		0.31
Mutation Taster		=288/12	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: rs371057703; hg19: chr6-126136529;