2-241230891-CCT-AGA

Variant names:

• chr2-241230891-CCT-AGA
• NM_005336.6:c.3340_3342delAGGinsTCT
• HDLBP p.Arg1114Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_005336.6(HDLBP):​c.3340_3342delAGGinsTCT​(p.Arg1114Ser) variant causes a missense change involving the alteration of a 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: 32)
• Consequence: HDLBP NM_005336.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.71
• Publications: 0 publications found

Genes affected

HDLBP (HGNC:4857): (high density lipoprotein binding protein) The protein encoded by this gene binds high density lipoprotein (HDL) and may function to regulate excess cholesterol levels in cells. The encoded protein also binds RNA and can induce heterochromatin formation. [provided by RefSeq, Mar 2016]

ANO7 (HGNC:31677): (anoctamin 7) This prostate-specific gene encodes a cytoplasmic protein, as well as a polytopic membrane protein which may serve as a target in prostate cancer diagnosis and immunotherapy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005336.6. 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
	HDLBP	NM_005336.6	MANE Select	c.3340_3342delAGGinsTCT	p.Arg1114Ser	missense	N/A	NP_005327.1	A0A024R4E5
	HDLBP	NM_001320965.3		c.3340_3342delAGGinsTCT	p.Arg1114Ser	missense	N/A	NP_001307894.1	Q00341-1
	HDLBP	NM_001320966.3		c.3340_3342delAGGinsTCT	p.Arg1114Ser	missense	N/A	NP_001307895.1	Q00341-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDLBP	ENST00000310931.10	TSL:1 MANE Select	c.3340_3342delAGGinsTCT	p.Arg1114Ser	missense	N/A	ENSP00000312042.4	Q00341-1
	HDLBP	ENST00000391975.5	TSL:1	c.3340_3342delAGGinsTCT	p.Arg1114Ser	missense	N/A	ENSP00000375836.1	Q00341-1
	HDLBP	ENST00000875612.1		c.3454_3456delAGGinsTCT	p.Arg1152Ser	missense	N/A	ENSP00000545671.1

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

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: chr2-242170306;