Variant 11-75667808-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000304771.8(MAP6):c.562G>A(p.Ala188Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,312,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

MAP6
ENST00000304771.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.568

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 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=0.20663533).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP6	NM_033063.2 linkuse as main transcript	c.562G>A	p.Ala188Thr	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.562G>A	p.Ala188Thr	missense_variant	1/4	1	NM_033063.2	ENSP00000307093	A2	Q96JE9-1
MAP6	ENST00000434603.2 linkuse as main transcript	c.562G>A	p.Ala188Thr	missense_variant	1/3	1		ENSP00000415108	P2	Q96JE9-2
MAP6	ENST00000526740.3 linkuse as main transcript	c.-83+722G>A		intron_variant		5		ENSP00000434278	A2	Q96JE9-3

Frequencies

GnomAD3 genomes

AF:

0.0000531

AC:

AN:

150652

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000195

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

GnomAD4 exome

AF:

0.00000689

AC:

AN:

1161822

Hom.:

Cov.:

AF XY:

0.00000712

AC XY:

AN XY:

561476

show subpopulations

Gnomad4 AFR exome

AF:

0.000296

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000214

GnomAD4 genome

AF:

0.0000531

AC:

AN:

150764

Hom.:

Cov.:

AF XY:

0.0000272

AC XY:

AN XY:

73642

show subpopulations

Gnomad4 AFR

AF:

0.000194

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

Bravo

AF:

0.0000756

ExAC

AF:

0.0000129

AC:

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

Dec 14, 2021

The c.562G>A (p.A188T) alteration is located in exon 1 (coding exon 1) of the MAP6 gene. This alteration results from a G to A substitution at nucleotide position 562, causing the alanine (A) at amino acid position 188 to be replaced by a threonine (T). 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

0.084

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.097

T;.

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.47

T;T

M_CAP

Pathogenic

0.68

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.62

N;N

REVEL

Benign

0.090

Sift

Benign

0.18

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.61

P;.

Vest4

0.12

MutPred

0.37

Gain of phosphorylation at A188 (P = 0.012);Gain of phosphorylation at A188 (P = 0.012);

MVP

0.16

MPC

2.4

ClinPred

0.16

GERP RS

2.6

Varity_R

0.042

gMVP

0.18

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