Variant 18-34794119-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001386795.1(DTNA):c.231C>G(p.Asn77Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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. N77D) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

DTNA
NM_001386795.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.304

Variant links:

Genes affected

DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DTNA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10053378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNA	NM_001386795.1 linkuse as main transcript	c.231C>G	p.Asn77Lys	missense_variant	4/23	ENST00000444659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNA	ENST00000444659.6 linkuse as main transcript	c.231C>G	p.Asn77Lys	missense_variant	4/23	5	NM_001386795.1	P3	Q9Y4J8-17

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251302

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.78

DANN

Benign

0.91

DEOGEN2

Benign

0.027

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

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.022

MetaRNN

Benign

0.10

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.2

L;L;L;.;.;L;L;L;L;L;L;L;.;L;L;L

MutationTaster

Benign

0.92

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

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.0

N;.;N;.;.;.;N;N;.;.;.;N;.;.;N;N

REVEL

Benign

0.098

Sift

Benign

0.22

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

Sift4G

Benign

0.15

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.27

B;.;B;.;.;.;.;.;.;B;B;B;.;.;B;B

Vest4

0.54

MutPred

0.40

Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);.;Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);Gain of ubiquitination at N77 (P = 0.0203);

MVP

0.61

MPC

0.52

ClinPred

0.073

GERP RS

-9.3

Varity_R

0.15

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over