1-232806048-G-A

Position:

• chr1-232806048-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019090.3(MAP10):​c.599G>A​(p.Arg200His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/17 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)
• Consequence: MAP10 NM_019090.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.182

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]

ACMG classification

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=0.07256225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP10	NM_019090.3	c.599G>A	p.Arg200His	missense_variant	1/1	ENST00000418460.4	NP_061963.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP10	ENST00000418460.4	c.599G>A	p.Arg200His	missense_variant	1/1	6	NM_019090.3	ENSP00000403208.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.1025G>A (p.R342H) 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 1025, causing the arginine (R) at amino acid position 342 to be replaced by a histidine (H). 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	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Uncertain	0.99
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.058	N
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.99	N
REVEL	Benign	0.030
Sift	Benign	0.25	T
Sift4G	Benign	0.16	T
Vest4		0.054
MVP		0.030
MPC		0.21
ClinPred		0.24	T
GERP RS		0.59
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-232941794;