15-43522919-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_002373.6(MAP1A):c.1446A>G(p.Gly482=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,686 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (7 hom.)
• Consequence: MAP1A NM_002373.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.341

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 15-43522919-A-G is Benign according to our data. Variant chr15-43522919-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 717737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.341 with no splicing effect.
• BS2: High AC in GnomAd at 223 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP1A	NM_002373.6	c.1446A>G	p.Gly482=	synonymous_variant	4/6	ENST00000300231.6
MAP1A	NM_001411089.1	c.2160A>G	p.Gly720=	synonymous_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP1A	ENST00000300231.6	c.1446A>G	p.Gly482=	synonymous_variant	4/6	5	NM_002373.6	P2
MAP1A	ENST00000382031.5	c.2160A>G	p.Gly720=	synonymous_variant	5/7	5		A2

Frequencies

GnomAD3 genomes AF: 0.00147 AC: 223 AN: 152110 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000472

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00271

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00143 AC: 354 AN: 247632 Hom.: 1 AF XY: 0.00149 AC XY: 200 AN XY: 134524

Gnomad AFR exome AF: 0.000650

Gnomad AMR exome AF: 0.000903

Gnomad ASJ exome AF: 0.0000998

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00135

Gnomad NFE exome AF: 0.00243

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00206 AC: 3004 AN: 1461458 Hom.: 7 Cov.: 36 AF XY: 0.00202 AC XY: 1468 AN XY: 727018

Gnomad4 AFR exome AF: 0.000687

Gnomad4 AMR exome AF: 0.000941

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00122

Gnomad4 NFE exome AF: 0.00249

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.00147 AC: 224 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.00134 AC XY: 100 AN XY: 74434

Gnomad4 AFR AF: 0.000554

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000472

Gnomad4 NFE AF: 0.00272

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00201 Hom.: 0

Bravo AF: 0.00119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	MAP1A: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	5.4
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs55941117; hg19: chr15-43815117;