rs1137524

Positions:

• chr3-47914934-C-G
• chr3-47914934-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385682.1(MAP4):​c.1882G>C​(p.Val628Leu) 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. 15/21 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. V628A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAP4 NM_001385682.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11068252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP4	NM_001385682.1	c.1882G>C	p.Val628Leu	missense_variant	8/21	ENST00000683076.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP4	ENST00000683076.1	c.1882G>C	p.Val628Leu	missense_variant	8/21		NM_001385682.1	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.6
DANN	Benign	0.78
DEOGEN2	Benign	0.037	.;T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.040
Sift	Uncertain	0.0030	D;D;D
Sift4G	Benign	0.35	T;T;T
Polyphen		0.61	P;.;D
Vest4		0.17
MutPred		0.13		Gain of glycosylation at T627 (P = 0.0106);.;Gain of glycosylation at T627 (P = 0.0106);
MVP		0.093
MPC		0.098
ClinPred		0.20	T
GERP RS		0.42
Varity_R		0.088
gMVP		0.049

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1137524; hg19: chr3-47956424;