NM_001385682.1:c.6743C>A

Variant names:

• chr3-47853306-G-T
• rs2047393255
• NM_001385682.1:c.6743C>A

Variant summary

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

The NM_001385682.1(MAP4):​c.6743C>A​(p.Ala2248Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAP4 NM_001385682.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.77
• Publications: 0 publications found

Genes affected

MAP4 (HGNC:6862): (microtubule associated protein 4) The protein encoded by this gene is a major non-neuronal microtubule-associated protein. This protein contains a domain similar to the microtubule-binding domains of neuronal microtubule-associated protein (MAP2) and microtubule-associated protein tau (MAPT/TAU). This protein promotes microtubule assembly, and has been shown to counteract destabilization of interphase microtubule catastrophe promotion. Cyclin B was found to interact with this protein, which targets cell division cycle 2 (CDC2) kinase to microtubules. The phosphorylation of this protein affects microtubule properties and cell cycle progression. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

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=0.20368075).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385682.1. 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
	MAP4	NM_001385682.1	MANE Select	c.6743C>A	p.Ala2248Asp	missense	Exon 20 of 21	NP_001372611.1	A0A804HKE7
	MAP4	NM_001385687.1		c.6743C>A	p.Ala2248Asp	missense	Exon 20 of 21	NP_001372616.1
	MAP4	NM_001385689.1		c.6629C>A	p.Ala2210Asp	missense	Exon 19 of 20	NP_001372618.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP4	ENST00000683076.1	MANE Select	c.6743C>A	p.Ala2248Asp	missense	Exon 20 of 21	ENSP00000507895.1	A0A804HKE7
	MAP4	ENST00000360240.10	TSL:1	c.3308C>A	p.Ala1103Asp	missense	Exon 18 of 19	ENSP00000353375.6	P27816-1
	MAP4	ENST00000429422.5	TSL:1	c.1331C>A	p.Ala444Asp	missense	Exon 9 of 10	ENSP00000416743.1	H7C4C5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458886 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725696

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.0000225 AC: 1 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5146

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60250

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.29
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.051	T
Eigen	Benign	-0.0012
Eigen_PC	Benign	0.076
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		2.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.056
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.025	D
Polyphen		0.98	D
Vest4		0.61
MutPred		0.14		Loss of glycosylation at P2244 (P = 0.0286)
MVP		0.22
MPC		0.48
ClinPred		0.92	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.52
gMVP		0.26
Mutation Taster		=92/8	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: rs2047393255; hg19: chr3-47894796;