19-13135305-CAGT-C

Position:

• chr19-13135305-CAGT-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The ENST00000292431.5(NACC1):​c.99_101del​(p.Val36del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NACC1 ENST00000292431.5 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.21

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in ENST00000292431.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NACC1	NM_052876.4	c.99_101del	p.Val36del	inframe_deletion	2/6	ENST00000292431.5	NP_443108.1
NACC1	XM_005259721.4	c.99_101del	p.Val36del	inframe_deletion	3/7		XP_005259778.1
NACC1	XM_047438118.1	c.99_101del	p.Val36del	inframe_deletion	2/6		XP_047294074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NACC1	ENST00000292431.5	c.99_101del	p.Val36del	inframe_deletion	2/6	1	NM_052876.4	ENSP00000292431	P1
NACC1	ENST00000586171.3	c.99_101del	p.Val36del	inframe_deletion	3/7	5		ENSP00000467120	P1
NACC1	ENST00000700232.1	c.99_101del	p.Val36del	inframe_deletion	2/6			ENSP00000514870	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 05, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1492495). This variant has not been reported in the literature in individuals affected with NACC1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.99_101del, results in the deletion of 1 amino acid(s) of the NACC1 protein (p.Val36del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

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: chr19-13246119;