15-43525206-G-A

Position:

• chr15-43525206-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002373.6(MAP1A):​c.3733G>A​(p.Asp1245Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,940 control chromosomes in the GnomAD database, including 27,822 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1837 hom., cov: 32)
  • Exomes 𝑓: 0.18 (25985 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011022091).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP1A	NM_002373.6	c.3733G>A	p.Asp1245Asn	missense_variant	4/6	ENST00000300231.6	NP_002364.5
MAP1A	NM_001411089.1	c.4447G>A	p.Asp1483Asn	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>A	p.Asp1245Asn	missense_variant	4/6	5	NM_002373.6	ENSP00000300231	P2
MAP1A	ENST00000382031.5	c.4447G>A	p.Asp1483Asn	missense_variant	5/7	5		ENSP00000371462	A2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21834 AN: 152020 Hom.: 1841 Cov.: 32

Gnomad AFR AF: 0.0795

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.164

GnomAD3 exomes AF: 0.155 AC: 38594 AN: 248796 Hom.: 3531 AF XY: 0.163 AC XY: 22055 AN XY: 135076

Gnomad AFR exome AF: 0.0776

Gnomad AMR exome AF: 0.100

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.00245

Gnomad SAS exome AF: 0.207

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.191

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.181 AC: 265221 AN: 1461800 Hom.: 25985 Cov.: 54 AF XY: 0.183 AC XY: 133319 AN XY: 727204

Gnomad4 AFR exome AF: 0.0754

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.00144

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.143 AC: 21826 AN: 152140 Hom.: 1837 Cov.: 32 AF XY: 0.140 AC XY: 10432 AN XY: 74366

Gnomad4 AFR AF: 0.0794

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.162

Alfa AF: 0.181 Hom.: 5365

Bravo AF: 0.140

TwinsUK AF: 0.193 AC: 716

ALSPAC AF: 0.184 AC: 711

ESP6500AA AF: 0.0773 AC: 332

ESP6500EA AF: 0.189 AC: 1600

ExAC AF: 0.156 AC: 18889

Asia WGS AF: 0.0790 AC: 279 AN: 3478

EpiCase AF: 0.196

EpiControl AF: 0.194

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	0.047
Eigen_PC	Benign	-0.028
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.85	D;D
MetaRNN	Benign	0.0011	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.9	.;L
MutationTaster	Benign	0.95	P;P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.015	D;D
Polyphen		0.83	.;P
Vest4		0.13
MPC		0.64
ClinPred		0.024	T
GERP RS		4.0
Varity_R		0.11
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

LitVar

Other links and lift over

dbSNP: rs12912505; hg19: chr15-43817404; COSMIC: COSV55808900;