Genetic Variant MAP10:c.-9G>A (chr1-232805441-G-A) – 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.-9G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,459,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

MAP10
NM_019090.3 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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=0.06426439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAP10	NM_019090.3 link	c.-9G>A		5_prime_UTR_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 link	c.-9G>A		5_prime_UTR_variant	Exon 1 of 1		NM_019090.3	ENSP00000403208.2		Q9P2G4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000111

AC:

AN:

242562

Hom.:

AF XY:

0.0000757

AC XY:

AN XY:

132054

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:

0.000795

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000919

Gnomad OTH exome

AF:

0.000337

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1459396

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

725814

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000430

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000662

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.418G>A (p.A140T) alteration is located in exon 1 (coding exon 1) of the MAP10 gene. This alteration results from a G to A substitution at nucleotide position 418, causing the alanine (A) at amino acid position 140 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

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.62

M_CAP

Benign

0.0065

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.59

REVEL

Benign

0.029

Sift

Uncertain

0.023

Sift4G

Benign

0.083

Vest4

0.17

MutPred

0.21

Gain of loop (P = 0.024);

MVP

0.12

MPC

0.39

ClinPred

0.45

GERP RS

3.0

gMVP

0.055

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