rs372864638

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001387751.1(DMTN):​c.107A>C​(p.Asn36Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

DMTN
NM_001387751.1 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.53
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36613178).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DMTNNM_001387751.1 linkc.107A>C p.Asn36Thr missense_variant Exon 4 of 16 ENST00000358242.6 NP_001374680.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DMTNENST00000358242.6 linkc.107A>C p.Asn36Thr missense_variant Exon 4 of 16 5 NM_001387751.1 ENSP00000350977.3 Q08495-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461854
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.0080
T
BayesDel_noAF
Benign
-0.25
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.052
T;.;.;.;T;.;.;.;T;T;.;T;T;.;T;T;.;.;.;T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.94
D;D;D;D;.;.;D;D;D;D;.;.;.;D;D;.;.;.;D;D
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.37
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.6
.;.;.;M;M;.;.;.;.;.;.;M;M;.;M;M;M;M;.;.
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-4.8
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;.
REVEL
Benign
0.24
Sift
Uncertain
0.0020
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;.
Sift4G
Uncertain
0.0080
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
0.86, 0.049
.;.;.;P;B;.;.;.;.;.;.;B;B;.;B;B;P;P;.;.
Vest4
0.54, 0.47, 0.54, 0.55, 0.53, 0.47, 0.67, 0.67, 0.46, 0.54, 0.53
MutPred
0.21
.;.;Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);.;.;.;.;.;Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);Gain of glycosylation at N36 (P = 0.1282);.;
MVP
0.56
MPC
0.37
ClinPred
0.98
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.35
gMVP
0.39

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.

Other links and lift over

hg19: chr8-21925051; API