NM_001039580.2:c.1352G>T

Variant names:

• chr4-155355099-C-A
• rs372432255
• NM_001039580.2:c.1352G>T

Variant summary

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

The NM_001039580.2(MAP9):​c.1352G>T​(p.Ser451Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,258,586 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S451N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: MAP9 NM_001039580.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.973
• Publications: 0 publications found

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

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=0.2404615).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039580.2. 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
	MAP9	NM_001039580.2	MANE Select	c.1352G>T	p.Ser451Ile	missense	Exon 10 of 14	NP_001034669.1	Q49MG5-1
	MAP9-AS1	NR_125937.1		n.158+726C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP9	ENST00000311277.9	TSL:1 MANE Select	c.1352G>T	p.Ser451Ile	missense	Exon 10 of 14	ENSP00000310593.4	Q49MG5-1
	MAP9	ENST00000433024.5	TSL:1	c.1349G>T	p.Ser450Ile	missense	Exon 10 of 11	ENSP00000394048.1	A2VCS9
	MAP9	ENST00000650955.1		c.1352G>T	p.Ser451Ile	missense	Exon 10 of 14	ENSP00000498412.1	Q49MG5-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1258586 Hom.: 0 Cov.: 19 AF XY: 0.00000317 AC XY: 2 AN XY: 630266

African (AFR) AF: 0.00 AC: 0 AN: 24428

American (AMR) AF: 0.00 AC: 0 AN: 28992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23266

East Asian (EAS) AF: 0.00 AC: 0 AN: 32304

South Asian (SAS) AF: 0.00 AC: 0 AN: 69696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5326

European-Non Finnish (NFE) AF: 0.00000206 AC: 2 AN: 971612

Other (OTH) AF: 0.00 AC: 0 AN: 52378

GnomAD4 genome Cov.: 33

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.97
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.11
Sift	Benign	0.046	D
Sift4G	Benign	0.12	T
Polyphen		0.95	P
Vest4		0.29
MutPred		0.35		Gain of helix (P = 0.0117)
MVP		0.35
MPC		0.29
ClinPred		0.93	D
GERP RS		4.2
Varity_R		0.17
gMVP		0.089
Mutation Taster		=89/11	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: rs372432255; hg19: chr4-156276251;