Variant chr11-75667829-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033063.2(MAP6):c.541T>G(p.Ser181Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000819 in 1,343,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MAP6
NM_033063.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.155

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033233106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP6	NM_033063.2 linkuse as main transcript	c.541T>G	p.Ser181Ala	missense_variant	1/4	ENST00000304771.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP6	ENST00000304771.8 linkuse as main transcript	c.541T>G	p.Ser181Ala	missense_variant	1/4	1	NM_033063.2	A2	Q96JE9-1
MAP6	ENST00000434603.2 linkuse as main transcript	c.541T>G	p.Ser181Ala	missense_variant	1/3	1		P2	Q96JE9-2
MAP6	ENST00000526740.3 linkuse as main transcript	c.-83+701T>G		intron_variant		5		A2	Q96JE9-3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151334

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

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:

0.00000755

AC:

AN:

1192358

Hom.:

Cov.:

AF XY:

0.00000517

AC XY:

AN XY:

580712

show subpopulations

Gnomad4 AFR exome

AF:

0.000165

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:

0.00000307

Gnomad4 OTH exome

AF:

0.0000417

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151334

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73910

show subpopulations

Gnomad4 AFR

AF:

0.0000485

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:

0.00000756

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

Aug 09, 2021

The c.541T>G (p.S181A) alteration is located in exon 1 (coding exon 1) of the MAP6 gene. This alteration results from a T to G substitution at nucleotide position 541, causing the serine (S) at amino acid position 181 to be replaced by an alanine (A). 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

0.063

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.65

DANN

Benign

0.40

DEOGEN2

Benign

0.034

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.25

T;T

M_CAP

Benign

0.072

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.76

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.11

N;N

REVEL

Benign

0.016

Sift

Benign

0.98

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.057

MutPred

0.32

Loss of glycosylation at S181 (P = 0.0055);Loss of glycosylation at S181 (P = 0.0055);

MVP

0.16

MPC

1.4

ClinPred

0.028

GERP RS

-0.85

Varity_R

0.045

gMVP

0.15

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