rs746021803

Variant names:

• chr4-155347841-C-T
• rs746021803
• NM_001039580.2:c.1886G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001039580.2(MAP9):​c.1886G>A​(p.Ser629Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAP9 NM_001039580.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.330
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023952246).
• BP6: Variant 4-155347841-C-T is Benign according to our data. Variant chr4-155347841-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3293181.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1886G>A	p.Ser629Asn	missense	Exon 14 of 14	NP_001034669.1	Q49MG5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP9	ENST00000311277.9	TSL:1 MANE Select	c.1886G>A	p.Ser629Asn	missense	Exon 14 of 14	ENSP00000310593.4	Q49MG5-1
	MAP9	ENST00000650955.1		c.1886G>A	p.Ser629Asn	missense	Exon 14 of 14	ENSP00000498412.1	Q49MG5-1
	MAP9	ENST00000933329.1		c.1886G>A	p.Ser629Asn	missense	Exon 14 of 14	ENSP00000603388.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245526 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000560

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455624 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724188

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

African (AFR) AF: 0.00 AC: 0 AN: 33204

American (AMR) AF: 0.00 AC: 0 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39328

South Asian (SAS) AF: 0.00 AC: 0 AN: 85584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107884

Other (OTH) AF: 0.00 AC: 0 AN: 60102

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.060
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.6
DANN	Benign	0.84
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.52	N
PhyloP100		0.33
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.020
Sift	Benign	0.83	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.035
MutPred		0.16		Gain of glycosylation at S625 (P = 0.0036)
MVP		0.12
MPC		0.035
ClinPred		0.017	T
GERP RS		1.8
Varity_R		0.041
gMVP		0.028
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs746021803; hg19: chr4-156268993;