4-155347848-G-C

Variant summary

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

The NM_001039580.2(MAP9):c.1879C>G(p.Leu627Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000895 in 1,451,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: MAP9 NM_001039580.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

Genes affected

MAP9 (HGNC:26118): (microtubule associated protein 9) ASAP is a microtubule-associated protein required for spindle function, mitotic progression, and cytokinesis (Saffin et al., 2005 [PubMed 16049101]).[supplied by OMIM, Mar 2008]

MAP9-AS1 (HGNC:56110): (MAP9 antisense RNA 1)

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=0.18673345).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP9	NM_001039580.2	c.1879C>G	p.Leu627Val	missense_variant	14/14	ENST00000311277.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP9	ENST00000311277.9	c.1879C>G	p.Leu627Val	missense_variant	14/14	1	NM_001039580.2	P1
MAP9-AS1	ENST00000630664.2	n.209-6361G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000895 AC: 13 AN: 1451754 Hom.: 0 Cov.: 28 AF XY: 0.00000554 AC XY: 4 AN XY: 722350

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000118

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.1879C>G (p.L627V) alteration is located in exon 14 (coding exon 13) of the MAP9 gene. This alteration results from a C to G substitution at nucleotide position 1879, causing the leucine (L) at amino acid position 627 to be replaced by a valine (V). 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	0.097
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.080	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.068
Sift	Benign	0.065	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.95	P;.
Vest4		0.31
MutPred		0.18		Gain of glycosylation at S625 (P = 0.0036);.;
MVP		0.36
MPC		0.20
ClinPred		0.82	D
GERP RS		3.0
Varity_R		0.074
gMVP		0.096

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

Other links and lift over

dbSNP: rs1731337219; hg19: chr4-156269000;