4-155357499-A-C

Variant names:

• chr4-155357499-A-C
• rs777642425
• NM_001039580.2:c.1071T>G

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.1071T>G​(p.Asn357Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000521 in 1,536,854 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. N357H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000051 (0 hom.)
• Consequence: MAP9 NM_001039580.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.81
• 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=0.06963089).

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.1071T>G	p.Asn357Lys	missense	Exon 8 of 14	NP_001034669.1	Q49MG5-1
	MAP9-AS1	NR_125937.1		n.272+297A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP9	ENST00000311277.9	TSL:1 MANE Select	c.1071T>G	p.Asn357Lys	missense	Exon 8 of 14	ENSP00000310593.4	Q49MG5-1
	MAP9	ENST00000433024.5	TSL:1	c.1068T>G	p.Asn356Lys	missense	Exon 8 of 11	ENSP00000394048.1	A2VCS9
	MAP9	ENST00000650955.1		c.1071T>G	p.Asn357Lys	missense	Exon 8 of 14	ENSP00000498412.1	Q49MG5-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 249500 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000175

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: 0.00000506 AC: 7 AN: 1384692 Hom.: 0 Cov.: 24 AF XY: 0.00000577 AC XY: 4 AN XY: 693210

African (AFR) AF: 0.00 AC: 0 AN: 31836

American (AMR) AF: 0.000158 AC: 7 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25600

East Asian (EAS) AF: 0.00 AC: 0 AN: 39172

South Asian (SAS) AF: 0.00 AC: 0 AN: 84254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52874

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1043306

Other (OTH) AF: 0.00 AC: 0 AN: 57764

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.0000655 AC: 1 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000247 AC: 3

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	0.22
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.8
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.040
Sift	Benign	0.044	D
Sift4G	Benign	0.79	T
Polyphen		0.93	P
Vest4		0.20
MutPred		0.28		Gain of methylation at N357 (P = 0.0092)
MVP		0.52
MPC		0.19
ClinPred		0.28	T
GERP RS		0.91
Varity_R		0.078
gMVP		0.16
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs777642425; hg19: chr4-156278651;