rs61999321

Variant names:

• chr13-29324646-C-A
• rs61999321
• NM_001033602.4:c.2840C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-29324646-C-A
• chr13-29324646-C-T

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.2840C>A​(p.Thr947Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MTUS2 NM_001033602.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.524
• Publications: 13 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]

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=0.07554886).

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.2840C>A	p.Thr947Lys	missense	Exon 7 of 16	NP_001028774.3	Q5JR59-2
	MTUS2	NM_001384605.1		c.2840C>A	p.Thr947Lys	missense	Exon 7 of 16	NP_001371534.1	Q5JR59-2
	MTUS2	NM_001384606.1		c.2840C>A	p.Thr947Lys	missense	Exon 6 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.2840C>A	p.Thr947Lys	missense	Exon 7 of 16	ENSP00000483729.2	Q5JR59-2
	MTUS2	ENST00000948542.1		c.2840C>A	p.Thr947Lys	missense	Exon 7 of 16	ENSP00000618601.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1442174 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 715034

African (AFR) AF: 0.00 AC: 0 AN: 33250

American (AMR) AF: 0.00 AC: 0 AN: 41782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.00 AC: 0 AN: 39264

South Asian (SAS) AF: 0.00 AC: 0 AN: 82414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101912

Other (OTH) AF: 0.00 AC: 0 AN: 59804

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 268

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.96
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.52
PrimateAI	Benign	0.32	T
Sift4G	Uncertain	0.037	D
Vest4		0.18
MVP		0.055
ClinPred		0.44	T
GERP RS		3.9
Mutation Taster		=98/2	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs61999321; hg19: chr13-29898783;