chr8-17653271-T-G

Variant names:

• chr8-17653271-T-G
• rs201830393
• NM_001363059.2:c.3299A>C

Variant summary

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

The NM_001363059.2(MTUS1):​c.3299A>C​(p.Asn1100Thr) 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. 16/22 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. N1100S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTUS1 NM_001363059.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 1 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04743597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTUS1	NM_001363059.2	c.3299A>C	p.Asn1100Thr	missense_variant	Exon 12 of 15	ENST00000693296.1	NP_001349988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTUS1	ENST00000693296.1	c.3299A>C	p.Asn1100Thr	missense_variant	Exon 12 of 15		NM_001363059.2	ENSP00000509719.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.021
DANN	Benign	0.56
DEOGEN2	Benign	0.017	.;.;.;.;T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.71	T;T;T;T;T;.;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.047	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	.;.;.;.;N;.;.
PhyloP100		-2.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.6	N;N;N;N;N;N;.
REVEL	Benign	0.035
Sift	Benign	0.14	T;T;T;T;T;T;.
Sift4G	Benign	0.48	T;T;T;T;T;T;T
Polyphen		0.0, 0.0010, 0.0030	.;B;B;B;B;B;.
Vest4		0.19
MutPred		0.12		.;.;.;.;Gain of phosphorylation at N1100 (P = 0.05);.;.;
MVP		0.12
ClinPred		0.056	T
GERP RS		-11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.062
gMVP		0.11
Mutation Taster		=89/11	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: rs201830393; hg19: chr8-17510780;