11-75587517-C-T

Variant names:

• chr11-75587517-C-T
• rs1281893685
• NM_033063.2:c.1984G>A

Variant summary

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

The NM_033063.2(MAP6):​c.1984G>A​(p.Gly662Ser) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G662R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAP6 NM_033063.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• Publications: 1 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: 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=0.07884386).

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.1984G>A	p.Gly662Ser	missense	Exon 4 of 4	NP_149052.1	Q96JE9-1
	MAP6-AS1	NR_145823.1		n.86+4236C>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.1984G>A	p.Gly662Ser	missense	Exon 4 of 4	ENSP00000307093.3	Q96JE9-1
	MAP6	ENST00000950404.1		c.2023G>A	p.Gly675Ser	missense	Exon 5 of 5	ENSP00000620463.1
	MAP6	ENST00000950405.1		c.1573G>A	p.Gly525Ser	missense	Exon 2 of 2	ENSP00000620464.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251480 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		-0.0040
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.083
Sift	Benign	0.066	T
Sift4G	Benign	0.60	T
Polyphen		0.48	P
Vest4		0.097
MutPred		0.15		Gain of phosphorylation at G662 (P = 0.0723)
MVP		0.38
MPC		0.19
ClinPred		0.35	T
GERP RS		4.0
Varity_R		0.063
gMVP		0.043
Mutation Taster		=98/2	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: rs1281893685; hg19: chr11-75298562;