17-2395160-A-G

Position:

• chr17-2395160-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020310.3(MNT):​c.368T>C​(p.Leu123Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: MNT NM_020310.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.78

Genes affected

MNT (HGNC:7188): (MAX network transcriptional repressor) The Myc/Max/Mad network comprises a group of transcription factors that co-interact to regulate gene-specific transcriptional activation or repression. This gene encodes a protein member of the Myc/Max/Mad network. This protein has a basic-Helix-Loop-Helix-zipper domain (bHLHzip) with which it binds the canonical DNA sequence CANNTG, known as the E box, following heterodimerization with Max proteins. This protein is likely a transcriptional repressor and an antagonist of Myc-dependent transcriptional activation and cell growth. This protein represses transcription by binding to DNA binding proteins at its N-terminal Sin3-interaction domain. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MNT	NM_020310.3	c.368T>C	p.Leu123Pro	missense_variant	2/6	ENST00000174618.5	NP_064706.1
MNT	XM_011523868.3	c.392T>C	p.Leu131Pro	missense_variant	2/6		XP_011522170.1
MNT	XM_047436092.1	c.191T>C	p.Leu64Pro	missense_variant	2/6		XP_047292048.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MNT	ENST00000174618.5	c.368T>C	p.Leu123Pro	missense_variant	2/6	1	NM_020310.3	ENSP00000174618.4
MNT	ENST00000575394.1	c.73+5480T>C		intron_variant		4		ENSP00000476269.1
MNT	ENST00000574559.1	n.434T>C		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

The c.368T>C (p.L123P) alteration is located in exon 2 (coding exon 2) of the MNT gene. This alteration results from a T to C substitution at nucleotide position 368, causing the leucine (L) at amino acid position 123 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.67	T
M_CAP	Pathogenic	0.56	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.83	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.69
MutPred		0.21		Loss of sheet (P = 0.0181);
MVP		0.26
MPC		1.3
ClinPred		0.89	D
GERP RS		4.3
Varity_R		0.28
gMVP		0.33

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

Publications

LitVar

Other links and lift over

dbSNP: rs1597421159; hg19: chr17-2298454;