6-125874930-A-T

Variant names:

• chr6-125874930-A-T
• rs139662554
• NM_181782.5:c.313A>T

Variant summary

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

The NM_181782.5(NCOA7):​c.313A>T​(p.Met105Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,432 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. M105V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NCOA7 NM_181782.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.69
• 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]

RN7SKP56 (HGNC:45780): (RN7SK pseudogene 56)

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.313A>T	p.Met105Leu	missense_variant	Exon 4 of 16	ENST00000392477.7	NP_861447.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7	c.313A>T	p.Met105Leu	missense_variant	Exon 4 of 16	1	NM_181782.5	ENSP00000376269.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461432 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727076

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111660

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.041	T;T;T;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.81	.;T;T;D;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T;T;T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	2.0	M;M;.;.;.
PhyloP100		6.7
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.7	N;N;N;N;D
REVEL	Benign	0.17
Sift	Benign	0.11	T;T;T;D;D
Sift4G	Uncertain	0.041	D;D;D;D;D
Polyphen		0.98	D;D;.;.;.
Vest4		0.54
MutPred		0.36		Gain of methylation at K104 (P = 0.0329);Gain of methylation at K104 (P = 0.0329);Gain of methylation at K104 (P = 0.0329);.;Gain of methylation at K104 (P = 0.0329);
MVP		0.093
MPC		0.45
ClinPred		0.85	D
GERP RS		5.3
Varity_R		0.37
gMVP		0.35
Mutation Taster		=14/186	disease causing

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: rs139662554; hg19: chr6-126196076;