Variant rs12912505 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002373.6(MAP1A):c.3733G>A(p.Asp1245Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,940 control chromosomes in the GnomAD database, including 27,822 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.14 ( 1837 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25985 hom. )

Consequence

MAP1A
NM_002373.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.804

Variant links:

Genes affected

MAP1A (HGNC:6835): (microtubule associated protein 1A) This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1A heavy chain and LC2 light chain. Expression of this gene is almost exclusively in the brain. Studies of the rat microtubule-associated protein 1A gene suggested a role in early events of spinal cord development. [provided by RefSeq, Jul 2008]

MAP1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011022091).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP1A	NM_002373.6 linkuse as main transcript	c.3733G>A	p.Asp1245Asn	missense_variant	4/6	ENST00000300231.6	NP_002364.5
MAP1A	NM_001411089.1 linkuse as main transcript	c.4447G>A	p.Asp1483Asn	missense_variant	5/7		NP_001398018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP1A	ENST00000300231.6 linkuse as main transcript	c.3733G>A	p.Asp1245Asn	missense_variant	4/6	5	NM_002373.6	ENSP00000300231	P2	P78559-1
MAP1A	ENST00000382031.5 linkuse as main transcript	c.4447G>A	p.Asp1483Asn	missense_variant	5/7	5		ENSP00000371462	A2

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21834

AN:

152020

Hom.:

1841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0795

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.155

AC:

38594

AN:

248796

Hom.:

3531

AF XY:

0.163

AC XY:

22055

AN XY:

135076

show subpopulations

Gnomad AFR exome

AF:

0.0776

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.00245

Gnomad SAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.181

AC:

265221

AN:

1461800

Hom.:

25985

Cov.:

AF XY:

0.183

AC XY:

133319

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.0754

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.212

Gnomad4 EAS exome

AF:

0.00144

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.132

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.143

AC:

21826

AN:

152140

Hom.:

1837

Cov.:

AF XY:

0.140

AC XY:

10432

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0794

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.211

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.185

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.190

Gnomad4 OTH

AF:

0.162

Alfa

AF:

0.181

Hom.:

5365

Bravo

AF:

0.140

TwinsUK

AF:

0.193

AC:

716

ALSPAC

AF:

0.184

AC:

711

ESP6500AA

AF:

0.0773

AC:

332

ESP6500EA

AF:

0.189

AC:

1600

ExAC

AF:

0.156

AC:

18889

Asia WGS

AF:

0.0790

AC:

279

AN:

3478

EpiCase

AF:

0.196

EpiControl

AF:

0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

0.047

Eigen_PC

Benign

-0.028

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.85

D;D

MetaRNN

Benign

0.0011

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.9

.;L

MutationTaster

Benign

0.95

P;P;P

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.015

D;D

Polyphen

0.83

.;P

Vest4

0.13

MPC

0.64

ClinPred

0.024

GERP RS

4.0

Varity_R

0.11

gMVP

0.16

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over