Variant 11-75608173-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_033063.2(MAP6):c.1055A>G(p.Asn352Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000269 in 1,614,222 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 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

MAP6
NM_033063.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

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=0.16230565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP6	NM_033063.2 linkuse as main transcript	c.1055A>G	p.Asn352Ser	missense_variant	2/4	ENST00000304771.8	NP_149052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAP6	ENST00000304771.8 linkuse as main transcript	c.1055A>G	p.Asn352Ser	missense_variant	2/4	1	NM_033063.2	ENSP00000307093.3	Q96JE9-1
MAP6	ENST00000434603.2 linkuse as main transcript	c.1055A>G	p.Asn352Ser	missense_variant	2/3	1		ENSP00000415108.2	Q96JE9-2
MAP6	ENST00000526740.3 linkuse as main transcript	c.68A>G	p.Asn23Ser	missense_variant	2/4	5		ENSP00000434278.1	Q96JE9-3

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000323

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000195

AC:

AN:

251488

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000277

AC:

405

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

195

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000334

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000197

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000783

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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

Nov 22, 2023

The c.1055A>G (p.N352S) alteration is located in exon 2 (coding exon 2) of the MAP6 gene. This alteration results from a A to G substitution at nucleotide position 1055, causing the asparagine (N) at amino acid position 352 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

0.093

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

D;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.7

M;.;M

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.14

Sift

Benign

0.055

T;D;D

Sift4G

Benign

0.23

T;T;T

Polyphen

0.26

B;.;.

Vest4

0.55

MVP

0.48

MPC

0.31

ClinPred

0.061

GERP RS

0.73

Varity_R

0.067

gMVP

0.34

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