rs1025245959

Variant names:

• chr6-125855073-C-A
• rs1025245959
• NM_181782.5:c.104C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-125855073-C-A
• chr6-125855073-C-G
• chr6-125855073-C-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.104C>A​(p.Ala35Asp) 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. 15/22 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. A35G) 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: 0.718
• 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=0.09594852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOA7	NM_181782.5	c.104C>A	p.Ala35Asp	missense_variant	Exon 3 of 16	ENST00000392477.7	NP_861447.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOA7	ENST00000392477.7	c.104C>A	p.Ala35Asp	missense_variant	Exon 3 of 16	1	NM_181782.5	ENSP00000376269.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250390 AF XY: 0.00

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: 0.0000478

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.0086	T;T;.;T;.;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.71	.;T;.;T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.096	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;.;.;.;.
PhyloP100		0.72
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.32	N;N;D;N;D;N
REVEL	Benign	0.076
Sift	Uncertain	0.012	D;D;D;D;D;D
Sift4G	Benign	0.31	T;T;D;D;D;D
Polyphen		0.041	B;B;.;.;.;.
Vest4		0.48
MutPred		0.22		Loss of MoRF binding (P = 0.05);Loss of MoRF binding (P = 0.05);Loss of MoRF binding (P = 0.05);Loss of MoRF binding (P = 0.05);Loss of MoRF binding (P = 0.05);Loss of MoRF binding (P = 0.05);
MVP		0.043
MPC		0.25
ClinPred		0.14	T
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.37
Mutation Taster		=96/4	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: rs1025245959; hg19: chr6-126176219;