NM_033063.2:c.1798T>C

Variant names:

• chr11-75587703-A-G
• rs142947527
• NM_033063.2:c.1798T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_033063.2(MAP6):​c.1798T>C​(p.Ser600Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 1,610,490 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (5 hom.)
• Consequence: MAP6 NM_033063.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.13
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034073293).
• BP6: Variant 11-75587703-A-G is Benign according to our data. Variant chr11-75587703-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2355287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 5 gene

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.1798T>C	p.Ser600Pro	missense	Exon 4 of 4	NP_149052.1	Q96JE9-1
	MAP6-AS1	NR_145823.1		n.86+4422A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP6	ENST00000304771.8	TSL:1 MANE Select	c.1798T>C	p.Ser600Pro	missense	Exon 4 of 4	ENSP00000307093.3	Q96JE9-1
	MAP6	ENST00000950404.1		c.1837T>C	p.Ser613Pro	missense	Exon 5 of 5	ENSP00000620463.1
	MAP6	ENST00000950405.1		c.1387T>C	p.Ser463Pro	missense	Exon 2 of 2	ENSP00000620464.1

Frequencies

GnomAD3 genomes AF: 0.000389 AC: 58 AN: 149126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0155

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000597

Gnomad OTH AF: 0.000490

GnomAD2 exomes AF: 0.000700 AC: 176 AN: 251480 AF XY: 0.000625

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0144

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.000399 AC: 583 AN: 1461364 Hom.: 5 Cov.: 31 AF XY: 0.000407 AC XY: 296 AN XY: 726948

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0159 AC: 415 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.0000711 AC: 79 AN: 1111742

Other (OTH) AF: 0.00142 AC: 86 AN: 60364

GnomAD4 genome AF: 0.000389 AC: 58 AN: 149126 Hom.: 0 Cov.: 32 AF XY: 0.000344 AC XY: 25 AN XY: 72764

African (AFR) AF: 0.00 AC: 0 AN: 40298

American (AMR) AF: 0.00 AC: 0 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.0155 AC: 53 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 5050

South Asian (SAS) AF: 0.00 AC: 0 AN: 4608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.0000597 AC: 4 AN: 67034

Other (OTH) AF: 0.000490 AC: 1 AN: 2042

Alfa AF: 0.00112 Hom.: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00105 AC: 9

ExAC AF: 0.000568 AC: 69

EpiCase AF: 0.000273

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.055
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.016
DANN	Benign	0.73
DEOGEN2	Benign	0.039	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.0	N
PhyloP100		-3.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.0080
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.042
MVP		0.11
MPC		0.22
ClinPred		0.022	T
GERP RS		-2.5
Varity_R		0.035
gMVP		0.014
Mutation Taster		=99/1	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: rs142947527; hg19: chr11-75298748;