16-568340-CA-TC

Variant names:

• chr16-568340-CA-TC
• NM_001301159.2:c.293_294delCAinsTC
• NHLRC4 p.Ala98Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001301159.2(NHLRC4):​c.293_294delCAinsTC​(p.Ala98Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NHLRC4 NM_001301159.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 0 publications found

Genes affected

NHLRC4 (HGNC:26700): (NHL repeat containing 4) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein K48-linked ubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

PIGQ (HGNC:14135): (phosphatidylinositol glycan anchor biosynthesis class Q) This gene is involved in the first step in glycosylphosphatidylinositol (GPI)-anchor biosynthesis. The GPI-anchor is a glycolipid found on many blood cells and serves to anchor proteins to the cell surface. This gene encodes a N-acetylglucosaminyl transferase component that is part of the complex that catalyzes transfer of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc to phosphatidylinositol (PI). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2012]

PIGQ Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 77

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000297509 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301159.2. 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
	NHLRC4	NM_001301159.2	MANE Select	c.293_294delCAinsTC	p.Ala98Val	missense	N/A	NP_001288088.1	P0CG21
	NHLRC4	NM_176677.3		c.293_294delCAinsTC	p.Ala98Val	missense	N/A	NP_788850.1	P0CG21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NHLRC4	ENST00000424439.3	TSL:3 MANE Select	c.293_294delCAinsTC	p.Ala98Val	missense	N/A	ENSP00000410858.2	P0CG21
	NHLRC4	ENST00000540585.1	TSL:1	c.293_294delCAinsTC	p.Ala98Val	missense	N/A	ENSP00000442223.1	P0CG21
	PIGQ	ENST00000409527.6	TSL:2	c.-10+777_-10+778delCAinsTC		intron	N/A	ENSP00000386760.2	Q9BRB3-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-618340;