5-72107584-C-G

Position:

• chr5-72107584-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The ENST00000296755.12(MAP1B):​c.53C>G​(p.Ala18Gly) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAP1B ENST00000296755.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

Genes affected

MAP1B (HGNC:6836): (microtubule associated protein 1B) This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1B heavy chain and LC1 light chain. Gene knockout studies of the mouse microtubule-associated protein 1B gene suggested an important role in development and function of the nervous system. [provided by RefSeq, Jul 2008]

LOC105379028 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MAP1B. . Gene score misZ 2.5114 (greater than the threshold 3.09). Trascript score misZ 3.9037 (greater than threshold 3.09). GenCC has associacion of gene with periventricular nodular heterotopia, periventricular nodular heterotopia 9.
• BP4: Computational evidence support a benign effect (MetaRNN=0.045401216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAP1B	NM_005909.5	c.53C>G	p.Ala18Gly	missense_variant	1/7	ENST00000296755.12	NP_005900.2
LOC105379028	XR_001742727.3	n.4713+1191G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAP1B	ENST00000296755.12	c.53C>G	p.Ala18Gly	missense_variant	1/7	1	NM_005909.5	ENSP00000296755	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 11, 2021

The c.53C>G (p.A18G) alteration is located in exon 1 (coding exon 1) of the MAP1B gene. This alteration results from a C to G substitution at nucleotide position 53, causing the alanine (A) at amino acid position 18 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	.;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.045	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.69	.;N;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.26	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.64	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.048
MutPred		0.030		Loss of stability (P = 0.1582);Loss of stability (P = 0.1582);Loss of stability (P = 0.1582);
MVP		0.18
MPC		0.86
ClinPred		0.21	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.063
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-71403411;