21-37232410-CG-TT

Variant names:

• chr21-37232410-CG-TT
• NM_006052.2:c.473_474delCGinsAA
• VPS26C p.Thr158Lys

Variant summary

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

The NM_006052.2(VPS26C):​c.473_474delCGinsAA​(p.Thr158Lys) variant causes a missense change. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T158M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: VPS26C NM_006052.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.84
• Publications: 0 publications found

Genes affected

VPS26C (HGNC:3044): (VPS26 endosomal protein sorting factor C) The region of chromosome 21 between genes CBR and ERG (CBR-ERG region), which spans 2.5 Mb on 21q22.2, has been defined by analysis of patients with partial trisomy 21. It contributes significantly to the pathogenesis of many characteristics of Down syndrome, including morphological features, hypotonia, and cognitive disability. The DSCR3 (Down syndrome critical region gene 3) gene is found in this region and is predictated to contain eight exons. DSCR3 is expressed in most tissues examined. [provided by RefSeq, Jul 2008]

ENSG00000242553 (HGNC:):

DSCR9 (HGNC:16301): (Down syndrome critical region 9)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006052.2. 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
	VPS26C	NM_006052.2	MANE Select	c.473_474delCGinsAA	p.Thr158Lys	missense	N/A	NP_006043.1	O14972-1
	VPS26C	NM_001331022.1		c.392_393delCGinsAA	p.Thr131Lys	missense	N/A	NP_001317951.1	O14972-2
	VPS26C	NM_001331021.1		c.329_330delCGinsAA	p.Thr110Lys	missense	N/A	NP_001317950.1	A8MY26

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VPS26C	ENST00000309117.11	TSL:1 MANE Select	c.473_474delCGinsAA	p.Thr158Lys	missense	N/A	ENSP00000311399.6	O14972-1
	VPS26C	ENST00000399000.7	TSL:1	n.1292_1293delCGinsAA		non_coding_transcript_exon	Exon 5 of 10
	VPS26C	ENST00000488368.5	TSL:1	n.564_565delCGinsAA		non_coding_transcript_exon	Exon 6 of 9

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		4.8

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: chr21-38604711;