Variant 8-22067145-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001387751.1(DMTN):c.79C>T(p.Pro27Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,456,060 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DMTN
NM_001387751.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.70

Variant links:

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]

DMTN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DMTN	NM_001387751.1 link	c.79C>T	p.Pro27Ser	missense_variant	Exon 3 of 16	ENST00000358242.6	NP_001374680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DMTN	ENST00000358242.6 link	c.79C>T	p.Pro27Ser	missense_variant	Exon 3 of 16	5	NM_001387751.1	ENSP00000350977.3		Q08495-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456060

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724504

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000259

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.79C>T (p.P27S) alteration is located in exon 3 (coding exon 2) of the DMTN gene. This alteration results from a C to T substitution at nucleotide position 79, causing the proline (P) at amino acid position 27 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.47

.;.;T;.;T;T;.;T;T;.;.;.

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.91

D;D;.;.;.;.;D;D;.;.;.;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.60

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Pathogenic

3.3

.;M;M;.;M;M;.;M;M;M;M;.

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.7

D;D;D;D;D;D;D;D;D;D;D;.

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;.;D;D;.;D;D;D;D;.

Vest4

0.74, 0.74, 0.53, 0.54, 0.74, 0.74

MutPred

0.38

Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);Gain of phosphorylation at P27 (P = 0.0132);

MVP

0.61

MPC

1.0

ClinPred

1.0

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.75

gMVP

0.71

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over