chr4-155355874-A-T

Variant names:

• chr4-155355874-A-T
• rs372595354
• NM_001039580.2:c.1132T>A

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.1132T>A​(p.Ser378Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MAP9 NM_001039580.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27
• 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=0.1888991).

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.1132T>A	p.Ser378Thr	missense	Exon 9 of 14	NP_001034669.1	Q49MG5-1
	MAP9-AS1	NR_125937.1		n.159-1215A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP9	ENST00000311277.9	TSL:1 MANE Select	c.1132T>A	p.Ser378Thr	missense	Exon 9 of 14	ENSP00000310593.4	Q49MG5-1
	MAP9	ENST00000433024.5	TSL:1	c.1129T>A	p.Ser377Thr	missense	Exon 9 of 11	ENSP00000394048.1	A2VCS9
	MAP9	ENST00000650955.1		c.1132T>A	p.Ser378Thr	missense	Exon 9 of 14	ENSP00000498412.1	Q49MG5-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249098 AF XY: 0.00000742

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459602 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726308

African (AFR) AF: 0.00 AC: 0 AN: 33276

American (AMR) AF: 0.0000225 AC: 1 AN: 44348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26054

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110852

Other (OTH) AF: 0.00 AC: 0 AN: 60236

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	Benign	0.095
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.043	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.034
Sift	Benign	0.033	D
Sift4G	Benign	0.62	T
Polyphen		0.59	P
Vest4		0.33
MVP		0.47
MPC		0.22
ClinPred		0.61	D
GERP RS		4.1
Varity_R		0.097
gMVP		0.40
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: rs372595354; hg19: chr4-156277026;