13-29480260-G-A

Variant names:

• chr13-29480260-G-A
• rs1200171198
• NM_001033602.4:c.3295G>A

Variant summary

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

The NM_001033602.4(MTUS2):​c.3295G>A​(p.Glu1099Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,401,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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. E1099Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: MTUS2 NM_001033602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14
• Publications: 0 publications found

Genes affected

MTUS2 (HGNC:20595): (microtubule associated scaffold protein 2) Enables microtubule binding activity and protein homodimerization activity. Part of nucleus. Colocalizes with centrosome and cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

MTUS2-AS1 (HGNC:40924): (MTUS2 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=0.15419737).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033602.4. 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
	MTUS2	NM_001033602.4	MANE Select	c.3295G>A	p.Glu1099Lys	missense	Exon 10 of 16	NP_001028774.3	Q5JR59-2
	MTUS2	NM_001384605.1		c.3295G>A	p.Glu1099Lys	missense	Exon 10 of 16	NP_001371534.1	Q5JR59-2
	MTUS2	NM_001384606.1		c.3295G>A	p.Glu1099Lys	missense	Exon 9 of 15	NP_001371535.1	Q5JR59-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTUS2	ENST00000612955.6	TSL:5 MANE Select	c.3295G>A	p.Glu1099Lys	missense	Exon 10 of 16	ENSP00000483729.2	Q5JR59-2
	MTUS2	ENST00000380808.6	TSL:1	c.232G>A	p.Glu78Lys	missense	Exon 3 of 9	ENSP00000370186.2	Q5JR59-3
	MTUS2	ENST00000542829.1	TSL:1	c.-39G>A		5_prime_UTR	Exon 2 of 8	ENSP00000445403.1	Q5JR59-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.13e-7 AC: 1 AN: 1401552 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 691470

African (AFR) AF: 0.00 AC: 0 AN: 31748

American (AMR) AF: 0.00 AC: 0 AN: 36092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25202

East Asian (EAS) AF: 0.00 AC: 0 AN: 36030

South Asian (SAS) AF: 0.00 AC: 0 AN: 79358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5172

European-Non Finnish (NFE) AF: 9.25e-7 AC: 1 AN: 1080518

Other (OTH) AF: 0.00 AC: 0 AN: 58036

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	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.1
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.076
Sift	Benign	0.030	D
Sift4G	Benign	0.62	T
Polyphen		0.026	B
Vest4		0.18
MVP		0.061
ClinPred		0.90	D
GERP RS		5.4
Mutation Taster		=90/10	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: rs1200171198; hg19: chr13-30054397;