15-43522364-G-T

Variant names:

• chr15-43522364-G-T
• rs763622955
• NM_002373.6:c.891G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002373.6(MAP1A):​c.891G>T​(p.Lys297Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MAP1A NM_002373.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 3 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36302933).

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.891G>T	p.Lys297Asn	missense	Exon 4 of 6	NP_002364.5
	MAP1A	NM_001411089.1		c.1605G>T	p.Lys535Asn	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.891G>T	p.Lys297Asn	missense	Exon 4 of 6	ENSP00000300231.5	P78559-1
	MAP1A	ENST00000382031.5	TSL:5	c.1605G>T	p.Lys535Asn	missense	Exon 5 of 7	ENSP00000371462.1	E9PGC8

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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 Cov.: 34

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74364

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.3
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.13
Sift	Benign	0.036	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.40		Loss of methylation at K297 (P = 0.0077)
MVP		0.29
MPC		0.37
ClinPred		0.93	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.27
gMVP		0.56

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: rs763622955; hg19: chr15-43814562; COSMIC: COSV100289102;