Variant 4-155355129-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_001039580.2(MAP9):c.1322A>G(p.His441Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000721 in 1,248,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

MAP9
NM_001039580.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

Variant links:

Genes affected

MAP9 (HGNC:26118): (microtubule associated protein 9) ASAP is a microtubule-associated protein required for spindle function, mitotic progression, and cytokinesis (Saffin et al., 2005 [PubMed 16049101]).[supplied by OMIM, Mar 2008]

MAP9 links:

MAP9-AS1 (HGNC:56110): (MAP9 antisense RNA 1)

MAP9-AS1 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=0.18560407).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP9	NM_001039580.2 linkuse as main transcript	c.1322A>G	p.His441Arg	missense_variant	10/14	ENST00000311277.9
MAP9-AS1	NR_125937.1 linkuse as main transcript	n.158+756T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP9	ENST00000311277.9 linkuse as main transcript	c.1322A>G	p.His441Arg	missense_variant	10/14	1	NM_001039580.2	P1	Q49MG5-1
MAP9-AS1	ENST00000630664.2 linkuse as main transcript	n.373+756T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000163

AC:

AN:

183520

Hom.:

AF XY:

0.0000199

AC XY:

AN XY:

100750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000332

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000721

AC:

AN:

1248006

Hom.:

Cov.:

AF XY:

0.00000959

AC XY:

AN XY:

625466

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000307

Gnomad4 SAS exome

AF:

0.0000288

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000520

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

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

Jun 23, 2023

The c.1322A>G (p.H441R) alteration is located in exon 10 (coding exon 9) of the MAP9 gene. This alteration results from a A to G substitution at nucleotide position 1322, causing the histidine (H) at amino acid position 441 to be replaced by an arginine (R). 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

0.18

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.011

T;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.0032

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.6

N;N;D

REVEL

Benign

0.085

Sift

Benign

0.044

D;D;D

Sift4G

Benign

0.66

T;T;.

Polyphen

0.90

P;.;.

Vest4

0.17

MVP

0.37

MPC

0.22

ClinPred

0.35

GERP RS

3.9

Varity_R

0.13

gMVP

0.031

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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