8-22080820-AGG-TCA

Variant names:

• chr8-22080820-AGG-TCA
• NM_001387751.1:c.973_975delAGGinsTCA
• DMTN p.Arg325Ser

Variant summary

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

The NM_001387751.1(DMTN):​c.973_975delAGGinsTCA​(p.Arg325Ser) 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 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: DMTN NM_001387751.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16
• Publications: 0 publications found

Genes affected

DMTN (HGNC:3382): (dematin actin binding protein) The protein encoded by this gene is an actin binding and bundling protein that plays a structural role in erythrocytes, by stabilizing and attaching the spectrin/actin cytoskeleton to the erythrocyte membrane in a phosphorylation-dependent manner. This protein contains a core domain in the N-terminus, and a headpiece domain in the C-terminus that binds F-actin. When purified from erythrocytes, this protein exists as a trimer composed of two 48 kDa polypeptides and a 52 kDa polypeptide. The different subunits arise from alternative splicing in the 3' coding region, where the headpiece domain is located. Disruption of this gene has been correlated with the autosomal dominant Marie Unna hereditary hypotrichosis disease, while loss of heterozygosity of this gene is thought to play a role in prostate cancer progression. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2014]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387751.1. 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
	DMTN	NM_001387751.1	MANE Select	c.973_975delAGGinsTCA	p.Arg325Ser	missense	N/A	NP_001374680.1	Q08495-1
	DMTN	NM_001114135.5		c.973_975delAGGinsTCA	p.Arg325Ser	missense	N/A	NP_001107607.1	Q08495-1
	DMTN	NM_001114136.3		c.973_975delAGGinsTCA	p.Arg325Ser	missense	N/A	NP_001107608.1	Q08495-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DMTN	ENST00000358242.6	TSL:5 MANE Select	c.973_975delAGGinsTCA	p.Arg325Ser	missense	N/A	ENSP00000350977.3	Q08495-1
	DMTN	ENST00000265800.9	TSL:5	c.973_975delAGGinsTCA	p.Arg325Ser	missense	N/A	ENSP00000265800.5	Q08495-1
	DMTN	ENST00000432128.6	TSL:5	c.973_975delAGGinsTCA	p.Arg325Ser	missense	N/A	ENSP00000416111.1	Q08495-1

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		4.2

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: chr8-21938331;