NM_001363059.2:c.3799A>G

Variant names:

• chr8-17645940-T-C
• NM_001363059.2:c.3799A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001363059.2(MTUS1):​c.3799A>G​(p.Ile1267Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MTUS1 NM_001363059.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.146
• Publications: 0 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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.015324771).
• BP6: Variant 8-17645940-T-C is Benign according to our data. Variant chr8-17645940-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3218601.Status of the report is criteria_provided_single_submitter, 1 stars.

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.3799A>G	p.Ile1267Val	missense	Exon 15 of 15	NP_001349988.1	Q9ULD2-1
	MTUS1	NM_001001924.3		c.3799A>G	p.Ile1267Val	missense	Exon 15 of 15	NP_001001924.1	Q9ULD2-1
	MTUS1	NM_001363058.2		c.3799A>G	p.Ile1267Val	missense	Exon 16 of 16	NP_001349987.1	Q9ULD2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTUS1	ENST00000693296.1	MANE Select	c.3799A>G	p.Ile1267Val	missense	Exon 15 of 15	ENSP00000509719.1	Q9ULD2-1
	MTUS1	ENST00000262102.10	TSL:1	c.3799A>G	p.Ile1267Val	missense	Exon 15 of 15	ENSP00000262102.6	Q9ULD2-1
	MTUS1	ENST00000297488.10	TSL:1	c.1297A>G	p.Ile433Val	missense	Exon 10 of 10	ENSP00000297488.6	Q9ULD2-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.8
DANN	Benign	0.84
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.97	T
PhyloP100		-0.15
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.060	N
REVEL	Benign	0.043
Sift	Benign	0.70	T
Sift4G	Benign	0.92	T
Polyphen		0.0020	B
Vest4		0.0070
MutPred		0.041		Loss of catalytic residue at P1269 (P = 0.0417)
MVP		0.37
ClinPred		0.018	T
GERP RS		-2.6
Varity_R		0.029
gMVP		0.24
Mutation Taster		=94/6	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

hg19: chr8-17503449;