NM_019090.3:c.223C>A

Variant names:

• chr1-232805672-C-A
• rs367723585
• NM_019090.3:c.223C>A

Variant summary

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

The NM_019090.3(MAP10):​c.223C>A​(p.Pro75Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P75A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAP10 NM_019090.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814
• Publications: 1 publications found

Genes affected

MAP10 (HGNC:29265): (microtubule associated protein 10) Enables microtubule binding activity. Involved in microtubule cytoskeleton organization; positive regulation of cytokinesis; and regulation of microtubule-based process. Located in microtubule cytoskeleton and midbody. [provided by Alliance of Genome Resources, Apr 2022]

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=0.131358).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019090.3. 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
	MAP10	NM_019090.3	MANE Select	c.223C>A	p.Pro75Thr	missense	Exon 1 of 1	NP_061963.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAP10	ENST00000418460.4	TSL:6 MANE Select	c.223C>A	p.Pro75Thr	missense	Exon 1 of 1	ENSP00000403208.2	Q9P2G4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000460 AC: 1 AN: 217186 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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000104

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447446 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 719856

African (AFR) AF: 0.00 AC: 0 AN: 33244

American (AMR) AF: 0.00 AC: 0 AN: 43930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25844

East Asian (EAS) AF: 0.00 AC: 0 AN: 39294

South Asian (SAS) AF: 0.00 AC: 0 AN: 85118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109040

Other (OTH) AF: 0.00 AC: 0 AN: 59922

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Uncertain	0.98
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.26	N
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
PhyloP100		0.81
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.059
Sift	Benign	0.31	T
Sift4G	Uncertain	0.030	D
Vest4		0.21
MVP		0.17
MPC		0.61
ClinPred		0.70	D
GERP RS		1.9
PromoterAI		-0.075	Neutral
gMVP		0.23
Mutation Taster		=96/4	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: rs367723585; hg19: chr1-232941418;