19-13138252-C-A

Variant names:

• chr19-13138252-C-A
• NM_052876.4:c.1430C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052876.4(NACC1):​c.1430C>A​(p.Pro477His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NACC1 NM_052876.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.74

Genes affected

NACC1 (HGNC:20967): (nucleus accumbens associated 1) This gene encodes a member of the BTB/POZ protein family. BTB/POZ proteins are involved in several cellular processes including proliferation, apoptosis and transcription regulation. The encoded protein is a transcriptional repressor that plays a role in stem cell self-renewal and pluripotency maintenance. The encoded protein also suppresses transcription of the candidate tumor suppressor Gadd45GIP1, and expression of this gene may play a role in the progression of multiple types of cancer. A pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
NACC1	NM_052876.4	c.1430C>A	p.Pro477His	missense_variant	Exon 6 of 6	ENST00000292431.5	NP_443108.1
NACC1	XM_005259721.4	c.1430C>A	p.Pro477His	missense_variant	Exon 7 of 7		XP_005259778.1
NACC1	XM_047438118.1	c.1430C>A	p.Pro477His	missense_variant	Exon 6 of 6		XP_047294074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NACC1	ENST00000292431.5	c.1430C>A	p.Pro477His	missense_variant	Exon 6 of 6	1	NM_052876.4	ENSP00000292431.3
NACC1	ENST00000586171.3	c.1430C>A	p.Pro477His	missense_variant	Exon 7 of 7	5		ENSP00000467120.2
NACC1	ENST00000700232.1	c.1430C>A	p.Pro477His	missense_variant	Exon 6 of 6			ENSP00000514870.1
NACC1	ENST00000585663.1	c.131C>A	p.Pro44His	missense_variant	Exon 2 of 2	5		ENSP00000466017.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.5	D;.
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.45
MutPred		0.39		Gain of helix (P = 0.0143);.;
MVP		0.49
MPC		2.6
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.67
gMVP		0.97

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-13249066;