3-47852865-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001134364.2(MAP4):​c.3335G>A​(p.Arg1112His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,569,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

MAP4
NM_001134364.2 missense

Scores

3
12

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.49
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07937989).
BP6
Variant 3-47852865-C-T is Benign according to our data. Variant chr3-47852865-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653784.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MAP4NM_001385682.1 linkc.*69G>A 3_prime_UTR_variant Exon 21 of 21 ENST00000683076.1 NP_001372611.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MAP4ENST00000683076 linkc.*69G>A 3_prime_UTR_variant Exon 21 of 21 NM_001385682.1 ENSP00000507895.1 A0A804HKE7

Frequencies

GnomAD3 genomes
AF:
0.000217
AC:
33
AN:
152164
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000353
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000209
AC:
37
AN:
176950
Hom.:
0
AF XY:
0.000219
AC XY:
21
AN XY:
95674
show subpopulations
Gnomad AFR exome
AF:
0.000102
Gnomad AMR exome
AF:
0.000153
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000398
Gnomad FIN exome
AF:
0.0000590
Gnomad NFE exome
AF:
0.000385
Gnomad OTH exome
AF:
0.000418
GnomAD4 exome
AF:
0.000291
AC:
412
AN:
1416826
Hom.:
0
Cov.:
32
AF XY:
0.000291
AC XY:
204
AN XY:
701260
show subpopulations
Gnomad4 AFR exome
AF:
0.0000311
Gnomad4 AMR exome
AF:
0.000189
Gnomad4 ASJ exome
AF:
0.0000395
Gnomad4 EAS exome
AF:
0.0000272
Gnomad4 SAS exome
AF:
0.0000612
Gnomad4 FIN exome
AF:
0.0000397
Gnomad4 NFE exome
AF:
0.000343
Gnomad4 OTH exome
AF:
0.000323
GnomAD4 genome
AF:
0.000217
AC:
33
AN:
152282
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74456
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000353
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000303
Hom.:
0
Bravo
AF:
0.000215
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.000110
AC:
13

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

MAP4: BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
20
DANN
Uncertain
1.0
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.65
T;T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.079
T;T;T
MetaSVM
Benign
-0.88
T
PROVEAN
Benign
-0.49
N;N;N
REVEL
Benign
0.096
Sift
Benign
0.21
T;T;T
Sift4G
Benign
0.090
T;T;T
Polyphen
1.0
D;D;.
Vest4
0.25
MVP
0.44
ClinPred
0.026
T
GERP RS
3.8

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780981104; hg19: chr3-47894355; API