15-43522515-G-T

Variant names:

• chr15-43522515-G-T
• rs1197365728
• NM_002373.6:c.1042G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002373.6(MAP1A):​c.1042G>T​(p.Ala348Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,613,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. A348T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MAP1A NM_002373.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19578958).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002373.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1A	NM_002373.6	MANE Select	c.1042G>T	p.Ala348Ser	missense	Exon 4 of 6	NP_002364.5
	MAP1A	NM_001411089.1		c.1756G>T	p.Ala586Ser	missense	Exon 5 of 7	NP_001398018.1	E9PGC8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP1A	ENST00000300231.6	TSL:5 MANE Select	c.1042G>T	p.Ala348Ser	missense	Exon 4 of 6	ENSP00000300231.5	P78559-1
	MAP1A	ENST00000382031.5	TSL:5	c.1756G>T	p.Ala586Ser	missense	Exon 5 of 7	ENSP00000371462.1	E9PGC8

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152072 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461328 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726894

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111722

Other (OTH) AF: 0.0000166 AC: 1 AN: 60378

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152072 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74272

African (AFR) AF: 0.0000483 AC: 2 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.051	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		4.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.56	N
REVEL	Benign	0.079
Sift	Benign	0.045	D
Sift4G	Benign	0.16	T
Polyphen		0.96	D
Vest4		0.33
MutPred		0.35		Gain of phosphorylation at A348 (P = 0.0017)
MVP		0.24
MPC		0.61
ClinPred		0.66	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.077
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

Other links and lift over

dbSNP: rs1197365728; hg19: chr15-43814713;