rs755292801

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015221.4(DNMBP):c.1978C>T(p.Pro660Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 1,600,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DNMBP
NM_015221.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0250

Publications

0 publications found

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:

DNMBP-AS1 (HGNC:20431): (DNMBP antisense RNA 1)

DNMBP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049914718).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMBP	NM_015221.4 link	c.1978C>T	p.Pro660Ser	missense_variant	Exon 4 of 17	ENST00000324109.9	NP_056036.1	Q6XZF7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNMBP	ENST00000324109.9 link	c.1978C>T	p.Pro660Ser	missense_variant	Exon 4 of 17	1	NM_015221.4	ENSP00000315659.4	Q6XZF7-1
DNMBP-AS1	ENST00000434409.2 link	n.173-178G>A		intron_variant	Intron 2 of 4	2
DNMBP-AS1	ENST00000661150.1 link	n.177-1293G>A		intron_variant	Intron 2 of 2
DNMBP-AS1	ENST00000661385.1 link	n.223-986G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152150

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

GnomAD2 exomes

AF:

0.00000416

AC:

AN:

240652

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000622

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1448116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718900

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32842

American (AMR)

AF:

0.00

AC:

AN:

42798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25310

East Asian (EAS)

AF:

0.00

AC:

AN:

39516

South Asian (SAS)

AF:

0.00

AC:

AN:

84402

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

9.05e-7

AC:

AN:

1104870

Other (OTH)

AF:

0.00

AC:

AN:

59654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 01, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1978C>T (p.P660S) alteration is located in exon 4 (coding exon 3) of the DNMBP gene. This alteration results from a C to T substitution at nucleotide position 1978, causing the proline (P) at amino acid position 660 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

Benign

0.076

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.027

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.59

M_CAP

Benign

0.0051

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

PhyloP100

0.025

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.9

REVEL

Benign

0.046

Sift

Benign

0.15

Sift4G

Benign

0.37

Polyphen

0.0010

Vest4

0.045

MutPred

0.14

Gain of MoRF binding (P = 0.0539);

MVP

0.53

MPC

0.14

ClinPred

0.055

GERP RS

1.3

Varity_R

0.037

gMVP

0.30

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs755292801

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over