8-17754450-T-G

Variant names:

• chr8-17754450-T-G
• rs17690844
• NM_001363059.2:c.1358A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363059.2(MTUS1):​c.1358A>C​(p.Lys453Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 1,614,176 control chromosomes in the GnomAD database, including 2,793 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.072 (725 hom., cov: 33)
  • Exomes 𝑓: 0.035 (2068 hom.)
• Consequence: MTUS1 NM_001363059.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 11 publications found

Genes affected

MTUS1 (HGNC:29789): (microtubule associated scaffold protein 1) This gene encodes a protein which contains a C-terminal domain able to interact with the angiotension II (AT2) receptor and a large coiled-coil region allowing dimerization. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the transcript variants has been shown to encode a mitochondrial protein that acts as a tumor suppressor and partcipates in AT2 signaling pathways. Other variants may encode nuclear or transmembrane proteins but it has not been determined whether they also participate in AT2 signaling pathways. [provided by RefSeq, Jul 2008]

ENSG00000301996 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0012432039).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363059.2. 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
	MTUS1	NM_001363059.2	MANE Select	c.1358A>C	p.Lys453Thr	missense	Exon 2 of 15	NP_001349988.1	Q9ULD2-1
	MTUS1	NM_001363057.2		c.1358A>C	p.Lys453Thr	missense	Exon 2 of 15	NP_001349986.1
	MTUS1	NM_001001924.3		c.1358A>C	p.Lys453Thr	missense	Exon 2 of 15	NP_001001924.1	Q9ULD2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTUS1	ENST00000693296.1	MANE Select	c.1358A>C	p.Lys453Thr	missense	Exon 2 of 15	ENSP00000509719.1	Q9ULD2-1
	MTUS1	ENST00000262102.10	TSL:1	c.1358A>C	p.Lys453Thr	missense	Exon 2 of 15	ENSP00000262102.6	Q9ULD2-1
	MTUS1	ENST00000520196.5	TSL:1	n.560A>C		non_coding_transcript_exon	Exon 1 of 15	ENSP00000431016.1	H0YC63

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10972 AN: 152178 Hom.: 720 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.0419

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.0597

GnomAD2 exomes AF: 0.0464 AC: 11579 AN: 249570 AF XY: 0.0419

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.0482

Gnomad ASJ exome AF: 0.00486

Gnomad EAS exome AF: 0.184

Gnomad FIN exome AF: 0.0401

Gnomad NFE exome AF: 0.0223

Gnomad OTH exome AF: 0.0308

GnomAD4 exome AF: 0.0345 AC: 50485 AN: 1461880 Hom.: 2068 Cov.: 72 AF XY: 0.0332 AC XY: 24154 AN XY: 727238

African (AFR) AF: 0.168 AC: 5618 AN: 33478

American (AMR) AF: 0.0487 AC: 2176 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00398 AC: 104 AN: 26136

East Asian (EAS) AF: 0.221 AC: 8761 AN: 39700

South Asian (SAS) AF: 0.0128 AC: 1108 AN: 86256

European-Finnish (FIN) AF: 0.0395 AC: 2108 AN: 53418

Middle Eastern (MID) AF: 0.0198 AC: 114 AN: 5768

European-Non Finnish (NFE) AF: 0.0252 AC: 28039 AN: 1112004

Other (OTH) AF: 0.0407 AC: 2457 AN: 60396

GnomAD4 genome AF: 0.0722 AC: 11000 AN: 152296 Hom.: 725 Cov.: 33 AF XY: 0.0731 AC XY: 5446 AN XY: 74478

African (AFR) AF: 0.163 AC: 6779 AN: 41544

American (AMR) AF: 0.0530 AC: 811 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3466

East Asian (EAS) AF: 0.203 AC: 1054 AN: 5180

South Asian (SAS) AF: 0.0147 AC: 71 AN: 4828

European-Finnish (FIN) AF: 0.0419 AC: 445 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0250 AC: 1700 AN: 68030

Other (OTH) AF: 0.0595 AC: 126 AN: 2116

Alfa AF: 0.0399 Hom.: 1263

Bravo AF: 0.0772

TwinsUK AF: 0.0235 AC: 87

ALSPAC AF: 0.0249 AC: 96

ESP6500AA AF: 0.157 AC: 588

ESP6500EA AF: 0.0286 AC: 236

ExAC AF: 0.0470 AC: 5678

Asia WGS AF: 0.0830 AC: 289 AN: 3478

EpiCase AF: 0.0236

EpiControl AF: 0.0219

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.64	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.4
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.020
Sift	Benign	0.15	T
Sift4G	Benign	0.17	T
Polyphen		0.041	B
Vest4		0.12
ClinPred		0.0073	T
GERP RS		2.5
Varity_R		0.069
gMVP		0.090
Mutation Taster		=95/5	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs17690844; hg19: chr8-17611959; COSMIC: COSV50551581; COSMIC: COSV50551581;