Genetic Variant MAP10:p.Leu25Val (chr1-232805522-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_019090.3(MAP10):c.73C>G(p.Leu25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,565,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/17 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: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

MAP10
NM_019090.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0990

Variant links:

Genes affected

MAP10 (HGNC:29265): (microtubule associated protein 10) Enables microtubule binding activity. Involved in microtubule cytoskeleton organization; positive regulation of cytokinesis; and regulation of microtubule-based process. Located in microtubule cytoskeleton and midbody. [provided by Alliance of Genome Resources, Apr 2022]

MAP10 links:

Genome browser will be placed here

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=0.041791946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP10	NM_019090.3 link	c.73C>G	p.Leu25Val	missense_variant	Exon 1 of 1	ENST00000418460.4	NP_061963.3	Q9P2G4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAP10	ENST00000418460.4 link	c.73C>G	p.Leu25Val	missense_variant	Exon 1 of 1	6	NM_019090.3	ENSP00000403208.2		Q9P2G4

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.00000589

AC:

AN:

169776

Hom.:

AF XY:

0.0000109

AC XY:

AN XY:

91338

show subpopulations

Gnomad AFR exome

AF:

0.000110

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000637

AC:

AN:

1413486

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698830

show subpopulations

Gnomad4 AFR exome

AF:

0.000247

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:

0.0000171

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.0000654

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:

0.0000453

ExAC

AF:

0.00000853

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.499C>G (p.L167V) alteration is located in exon 1 (coding exon 1) of the MAP10 gene. This alteration results from a C to G substitution at nucleotide position 499, causing the leucine (L) at amino acid position 167 to be replaced by a valine (V). 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

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

5.4

DANN

Benign

0.86

Eigen

Benign

-0.95

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.041

M_CAP

Benign

0.010

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.56

REVEL

Benign

0.040

Sift

Benign

0.11

Sift4G

Uncertain

0.049

Vest4

0.020

MVP

0.030

MPC

0.13

ClinPred

0.054

GERP RS

-0.99

gMVP

0.10

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