Variant 11-75667629-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000304771.8(MAP6):c.741T>G(p.Ile247Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,280,988 control chromosomes in the GnomAD database, including 199,595 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.55 ( 23233 hom., cov: 33)

Exomes 𝑓: 0.56 ( 176362 hom. )

Consequence

MAP6
ENST00000304771.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.795

Variant links:

Genes affected

MAP6 (HGNC:6868): (microtubule associated protein 6) This gene encodes a microtubule-associated protein. The encoded protein is a calmodulin-binding and calmodulin-regulated protein that is involved in microtubule stabilization. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MAP6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.982555E-6).

BP6

Variant 11-75667629-A-C is Benign according to our data. Variant chr11-75667629-A-C is described in ClinVar as [Benign]. Clinvar id is 1223129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP6	NM_033063.2 linkuse as main transcript	c.741T>G	p.Ile247Met	missense_variant	1/4	ENST00000304771.8	NP_149052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP6	ENST00000304771.8 linkuse as main transcript	c.741T>G	p.Ile247Met	missense_variant	1/4	1	NM_033063.2	ENSP00000307093	A2	Q96JE9-1
MAP6	ENST00000434603.2 linkuse as main transcript	c.741T>G	p.Ile247Met	missense_variant	1/3	1		ENSP00000415108	P2	Q96JE9-2
MAP6	ENST00000526740.3 linkuse as main transcript	c.-83+901T>G		intron_variant		5		ENSP00000434278	A2	Q96JE9-3

Frequencies

GnomAD3 genomes

AF:

0.552

AC:

83635

AN:

151396

Hom.:

23220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.573

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.555

Gnomad EAS

AF:

0.560

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.434

Gnomad MID

AF:

0.602

Gnomad NFE

AF:

0.552

Gnomad OTH

AF:

0.557

GnomAD3 exomes

AF:

0.538

AC:

272

AN:

506

Hom.:

AF XY:

0.532

AC XY:

166

AN XY:

312

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.500

Gnomad EAS exome

AF:

0.500

Gnomad SAS exome

AF:

0.429

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.560

Gnomad OTH exome

AF:

0.636

GnomAD4 exome

AF:

0.558

AC:

630121

AN:

1129484

Hom.:

176362

Cov.:

AF XY:

0.557

AC XY:

302842

AN XY:

543320

show subpopulations

Gnomad4 AFR exome

AF:

0.575

Gnomad4 AMR exome

AF:

0.561

Gnomad4 ASJ exome

AF:

0.559

Gnomad4 EAS exome

AF:

0.558

Gnomad4 SAS exome

AF:

0.532

Gnomad4 FIN exome

AF:

0.439

Gnomad4 NFE exome

AF:

0.562

Gnomad4 OTH exome

AF:

0.554

GnomAD4 genome

AF:

0.552

AC:

83695

AN:

151504

Hom.:

23233

Cov.:

AF XY:

0.549

AC XY:

40669

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.573

Gnomad4 AMR

AF:

0.562

Gnomad4 ASJ

AF:

0.555

Gnomad4 EAS

AF:

0.559

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.434

Gnomad4 NFE

AF:

0.552

Gnomad4 OTH

AF:

0.560

Alfa

AF:

0.545

Hom.:

2833

Bravo

AF:

0.564

TwinsUK

AF:

0.559

AC:

2074

ALSPAC

AF:

0.568

AC:

2189

ExAC

AF:

0.158

AC:

2167

Asia WGS

AF:

0.531

AC:

1780

AN:

3354

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.035

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.38

DEOGEN2

Benign

0.032

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.30

T;T

MetaRNN

Benign

0.0000060

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.0

N;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

1.0

N;N

REVEL

Benign

0.053

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.065

MPC

1.6

ClinPred

0.021

GERP RS

3.6

Varity_R

0.041

gMVP

0.13

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