NM_181782.5:c.155C>A

Variant names:

• chr6-125855124-C-A
• rs147393001
• NM_181782.5:c.155C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_181782.5(NCOA7):​c.155C>A​(p.Pro52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,612,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: NCOA7 NM_181782.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.19
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.031645417).
• BP6: Variant 6-125855124-C-A is Benign according to our data. Variant chr6-125855124-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3403563.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181782.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA7	NM_181782.5	MANE Select	c.155C>A	p.Pro52Gln	missense	Exon 3 of 16	NP_861447.3
	NCOA7	NM_001199619.2		c.155C>A	p.Pro52Gln	missense	Exon 4 of 17	NP_001186548.1	Q8NI08-1
	NCOA7	NM_001199620.2		c.155C>A	p.Pro52Gln	missense	Exon 5 of 18	NP_001186549.1	Q8NI08-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA7	ENST00000392477.7	TSL:1 MANE Select	c.155C>A	p.Pro52Gln	missense	Exon 3 of 16	ENSP00000376269.2	Q8NI08-1
	NCOA7	ENST00000368357.7	TSL:1	c.155C>A	p.Pro52Gln	missense	Exon 4 of 17	ENSP00000357341.3	Q8NI08-1
	NCOA7	ENST00000487635.1	TSL:1	n.292C>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151768 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250656 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000441

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000575 AC: 84 AN: 1461090 Hom.: 0 Cov.: 31 AF XY: 0.0000537 AC XY: 39 AN XY: 726884

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52960

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

European-Non Finnish (NFE) AF: 0.0000693 AC: 77 AN: 1111754

Other (OTH) AF: 0.0000994 AC: 6 AN: 60374

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151768 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74078

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41274

American (AMR) AF: 0.00 AC: 0 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67968

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000582 Hom.: 0

Bravo AF: 0.0000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.9
DANN	Benign	0.54
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	N
PhyloP100		2.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.056
Sift	Benign	0.50	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.24
MVP		0.043
MPC		0.082
ClinPred		0.015	T
GERP RS		2.9
Varity_R		0.032
gMVP		0.16
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: rs147393001; hg19: chr6-126176270;