NM_033063.2:c.1749T>A

Variant names:

• chr11-75587752-A-T
• rs1231128
• NM_033063.2:c.1749T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033063.2(MAP6):​c.1749T>A​(p.Asp583Glu) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D583D) has been classified as Benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAP6 NM_033063.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.795
• Publications: 0 publications found

Genes affected

MAP6 (HGNC:6868): (microtubule associated protein 6) This gene encodes a microtubule-associated protein. The encoded protein is a calmodulin-binding and calmodulin-regulated protein that is involved in microtubule stabilization. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MAP6-AS1 (HGNC:58170):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049180895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033063.2. 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
	MAP6	NM_033063.2	MANE Select	c.1749T>A	p.Asp583Glu	missense	Exon 4 of 4	NP_149052.1	Q96JE9-1
	MAP6-AS1	NR_145823.1		n.86+4471A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP6	ENST00000304771.8	TSL:1 MANE Select	c.1749T>A	p.Asp583Glu	missense	Exon 4 of 4	ENSP00000307093.3	Q96JE9-1
	MAP6	ENST00000950404.1		c.1788T>A	p.Asp596Glu	missense	Exon 5 of 5	ENSP00000620463.1
	MAP6	ENST00000950405.1		c.1338T>A	p.Asp446Glu	missense	Exon 2 of 2	ENSP00000620464.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 57

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.3
DANN	Benign	0.83
DEOGEN2	Benign	0.25	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.80
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.043
Sift	Benign	0.25	T
Sift4G	Benign	0.78	T
Polyphen		0.0020	B
Vest4		0.049
MutPred		0.13		Gain of methylation at K582 (P = 0.2207)
MVP		0.16
MPC		0.19
ClinPred		0.064	T
GERP RS		-5.5
Varity_R		0.049
gMVP		0.016
Mutation Taster		=100/0	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: rs1231128; hg19: chr11-75298797;