NM_002373.6:c.499A>C

Variant names:

• chr15-43521972-A-C
• rs774598505
• NM_002373.6:c.499A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002373.6(MAP1A):​c.499A>C​(p.Asn167His) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAP1A NM_002373.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.15
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1805802).

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.499A>C	p.Asn167His	missense	Exon 4 of 6	NP_002364.5
	MAP1A	NM_001411089.1		c.1213A>C	p.Asn405His	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.499A>C	p.Asn167His	missense	Exon 4 of 6	ENSP00000300231.5	P78559-1
	MAP1A	ENST00000382031.5	TSL:5	c.1213A>C	p.Asn405His	missense	Exon 5 of 7	ENSP00000371462.1	E9PGC8

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000478

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00155 AC: 2218 AN: 1432184 Hom.: 0 Cov.: 34 AF XY: 0.00140 AC XY: 999 AN XY: 713598

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00125 AC: 41 AN: 32824

American (AMR) AF: 0.0000224 AC: 1 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.000540 AC: 14 AN: 25904

East Asian (EAS) AF: 0.000178 AC: 7 AN: 39400

South Asian (SAS) AF: 0.000479 AC: 41 AN: 85628

European-Finnish (FIN) AF: 0.0000376 AC: 2 AN: 53174

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5728

European-Non Finnish (NFE) AF: 0.00188 AC: 2039 AN: 1085514

Other (OTH) AF: 0.00118 AC: 70 AN: 59378

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000526 AC: 8 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5 AN XY: 74414

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67946

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Benign	0.70
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.0098
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		5.2
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.058
Sift	Benign	0.074	T
Sift4G	Uncertain	0.020	D
Polyphen		0.0010	B
Vest4		0.26
MutPred		0.22		Gain of catalytic residue at L169 (P = 0.0611)
MVP		0.29
MPC		0.20
ClinPred		0.30	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.20
gMVP		0.82
Mutation Taster		=88/12	polymorphism

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: rs774598505; hg19: chr15-43814170; COSMIC: COSV109419244;