rs201538729

Variant names:

• chr6-125885228-C-A
• rs201538729
• NM_181782.5:c.769C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-125885228-C-A
• chr6-125885228-C-G

Variant summary

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

The NM_181782.5(NCOA7):​c.769C>A​(p.Leu257Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L257V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NCOA7 NM_181782.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA7	NM_181782.5	c.769C>A	p.Leu257Met	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.769C>A	p.Leu257Met	missense_variant	Exon 8 of 16	1	NM_181782.5	ENSP00000376269.2
NCOA7	ENST00000368357.7	c.769C>A	p.Leu257Met	missense_variant	Exon 9 of 17	1		ENSP00000357341.3
NCOA7	ENST00000229634.13	c.457C>A	p.Leu153Met	missense_variant	Exon 7 of 15	2		ENSP00000229634.9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461764 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727186

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111912

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.014	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.91	.;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.5	M;M;.
PhyloP100		0.32
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0070	D;D;D
Sift4G	Benign	0.13	T;T;T
Polyphen		1.0	D;D;.
Vest4		0.70
MutPred		0.41		Gain of solvent accessibility (P = 0.0354);Gain of solvent accessibility (P = 0.0354);.;
MVP		0.082
MPC		0.47
ClinPred		0.79	D
GERP RS		-0.64
Varity_R		0.18
gMVP		0.66
Mutation Taster		=89/11	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: rs201538729; hg19: chr6-126206374;