chr15-43525206-G-C

Position:

• chr15-43525206-G-C

Variant summary

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

The NM_002373.6(MAP1A):​c.3733G>C​(p.Asp1245His) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1245N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP1A NM_002373.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804

Genes affected

MAP1A (HGNC:6835): (microtubule associated protein 1A) This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1A heavy chain and LC2 light chain. Expression of this gene is almost exclusively in the brain. Studies of the rat microtubule-associated protein 1A gene suggested a role in early events of spinal cord development. [provided by RefSeq, Jul 2008]

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=0.093492985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP1A	NM_002373.6	c.3733G>C	p.Asp1245His	missense_variant	4/6	ENST00000300231.6	NP_002364.5
MAP1A	NM_001411089.1	c.4447G>C	p.Asp1483His	missense_variant	5/7		NP_001398018.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP1A	ENST00000300231.6	c.3733G>C	p.Asp1245His	missense_variant	4/6	5	NM_002373.6	ENSP00000300231	P2
MAP1A	ENST00000382031.5	c.4447G>C	p.Asp1483His	missense_variant	5/7	5		ENSP00000371462	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 54

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.12	.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L
MutationTaster	Benign	0.82	P;P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.10
Sift	Benign	0.10	T;T
Sift4G	Benign	0.080	T;T
Polyphen		0.073	.;B
Vest4		0.26
MutPred		0.11		.;Loss of catalytic residue at D1245 (P = 0.1438);
MVP		0.13
MPC		0.79
ClinPred		0.23	T
GERP RS		4.0
Varity_R		0.13
gMVP		0.25

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

Other links and lift over

dbSNP: rs12912505; hg19: chr15-43817404;