Variant 10-99877332-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015221.4(DNMBP):c.4553A>G(p.Tyr1518Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000446 in 1,609,374 control chromosomes in the GnomAD database, including 8 homozygotes. 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: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 8 hom. )

Consequence

DNMBP
NM_015221.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.89

Variant links:

Genes affected

DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

DNMBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21488997).

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMBP	NM_015221.4 linkuse as main transcript	c.4553A>G	p.Tyr1518Cys	missense_variant	17/17	ENST00000324109.9	NP_056036.1	Q6XZF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNMBP	ENST00000324109.9 linkuse as main transcript	c.4553A>G	p.Tyr1518Cys	missense_variant	17/17	1	NM_015221.4	ENSP00000315659.4	Q6XZF7-1
DNMBP	ENST00000543621.6 linkuse as main transcript	c.2417A>G	p.Tyr806Cys	missense_variant	14/14	1		ENSP00000443657.2	A0A1C7CYY6
DNMBP	ENST00000636706.1 linkuse as main transcript	c.3449A>G	p.Tyr1150Cys	missense_variant	14/14	2		ENSP00000489875.1	A0A1B0GTX1

Frequencies

GnomAD3 genomes

AF:

0.000402

AC:

AN:

151730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000585

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000379

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000574

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000669

AC:

165

AN:

246774

Hom.:

AF XY:

0.000742

AC XY:

AN XY:

133468

show subpopulations

Gnomad AFR exome

AF:

0.0000619

Gnomad AMR exome

AF:

0.000483

Gnomad ASJ exome

AF:

0.000508

Gnomad EAS exome

AF:

0.000386

Gnomad SAS exome

AF:

0.00171

Gnomad FIN exome

AF:

0.000279

Gnomad NFE exome

AF:

0.000615

Gnomad OTH exome

AF:

0.00167

GnomAD4 exome

AF:

0.000450

AC:

656

AN:

1457524

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

360

AN XY:

724952

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000386

Gnomad4 ASJ exome

AF:

0.000270

Gnomad4 EAS exome

AF:

0.000203

Gnomad4 SAS exome

AF:

0.00197

Gnomad4 FIN exome

AF:

0.000506

Gnomad4 NFE exome

AF:

0.000339

Gnomad4 OTH exome

AF:

0.000565

GnomAD4 genome

AF:

0.000402

AC:

AN:

151850

Hom.:

Cov.:

AF XY:

0.000391

AC XY:

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000586

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000379

Gnomad4 NFE

AF:

0.000574

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000614

Hom.:

Bravo

AF:

0.000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000717

AC:

EpiCase

AF:

0.00110

EpiControl

AF:

0.000834

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2024

The c.4553A>G (p.Y1518C) alteration is located in exon 17 (coding exon 16) of the DNMBP gene. This alteration results from a A to G substitution at nucleotide position 4553, causing the tyrosine (Y) at amino acid position 1518 to be replaced by a cysteine (C). 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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.010

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

.;.;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.64

.;.;N

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-6.7

.;.;D

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0010

.;.;D

Polyphen

1.0

.;.;D

Vest4

0.78

MVP

0.87

MPC

0.70

ClinPred

0.10

GERP RS

5.4

Varity_R

0.86

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over