2-24658683-T-C

Variant names:

• chr2-24658683-T-C
• NM_003743.5:c.6T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6 BP7

The NM_003743.5(NCOA1):​c.6T>C​(p.Ser2Ser) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NCOA1 NM_003743.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.19
• Publications: 0 publications found

Genes affected

NCOA1 (HGNC:7668): (nuclear receptor coactivator 1) The protein encoded by this gene acts as a transcriptional coactivator for steroid and nuclear hormone receptors. It is a member of the p160/steroid receptor coactivator (SRC) family and like other family members has histone acetyltransferase activity and contains a nuclear localization signal, as well as bHLH and PAS domains. The product of this gene binds nuclear receptors directly and stimulates the transcriptional activities in a hormone-dependent fashion. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 2-24658683-T-C is Benign according to our data. Variant chr2-24658683-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3353797.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=3.19 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003743.5. 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
	NCOA1	NM_003743.5	MANE Select	c.6T>C	p.Ser2Ser	synonymous	Exon 5 of 23	NP_003734.3
	NCOA1	NM_147233.2		c.6T>C	p.Ser2Ser	synonymous	Exon 3 of 21	NP_671766.1	Q15788-3
	NCOA1	NM_001362950.1		c.6T>C	p.Ser2Ser	synonymous	Exon 5 of 24	NP_001349879.1	Q15788-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOA1	ENST00000348332.8	TSL:1 MANE Select	c.6T>C	p.Ser2Ser	synonymous	Exon 5 of 23	ENSP00000320940.5	Q15788-1
	NCOA1	ENST00000395856.3	TSL:1	c.6T>C	p.Ser2Ser	synonymous	Exon 3 of 21	ENSP00000379197.3	Q15788-3
	NCOA1	ENST00000288599.9	TSL:1	c.6T>C	p.Ser2Ser	synonymous	Exon 3 of 22	ENSP00000288599.5	Q15788-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NCOA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=233/67	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

hg19: chr2-24881552;