Genetic Variant MTCL3:p.Ile917Val (chr6-127473376-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001400265.1(MTCL3):c.2749A>G(p.Ile917Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 1,386,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

MTCL3
NM_001400265.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

Publications

1 publications found

Variant links:

Genes affected

MTCL3 (HGNC:21494): (MTCL family member 3) Predicted to be involved in regulation of autophagy. Predicted to be located in extracellular space. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MTCL3 links:

ENSG00000255330 (HGNC:):

ENSG00000255330 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27929714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001400265.1. 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
	MTCL3	NM_001400265.1	MANE Select	c.2749A>G	p.Ile917Val	missense	Exon 7 of 7	NP_001387194.1	Q5TF21
	SOGA3-KIAA0408	NR_174482.1		n.3594A>G		non_coding_transcript_exon	Exon 7 of 13

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTCL3	ENST00000525778.6	TSL:5 MANE Select	c.2749A>G	p.Ile917Val	missense	Exon 7 of 7	ENSP00000434570.1	Q5TF21
ENSG00000255330	ENST00000481848.6	TSL:5	n.2749A>G		non_coding_transcript_exon	Exon 7 of 12	ENSP00000455908.1
MTCL3	ENST00000465909.3	TSL:5	c.2740A>G	p.Ile914Val	missense	Exon 7 of 7	ENSP00000435559.1	E9PJP2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000539

AC:

AN:

185620

AF XY:

0.00000974

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000216

AC:

AN:

1386484

Hom.:

Cov.:

AF XY:

0.0000116

AC XY:

AN XY:

689096

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28298

American (AMR)

AF:

0.00

AC:

AN:

28380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24124

East Asian (EAS)

AF:

0.00

AC:

AN:

34214

South Asian (SAS)

AF:

0.00

AC:

AN:

74482

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5564

European-Non Finnish (NFE)

AF:

0.0000277

AC:

AN:

1081714

Other (OTH)

AF:

0.00

AC:

AN:

57098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

M_CAP

Benign

0.018

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

7.7

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.030

REVEL

Benign

0.11

Sift

Uncertain

0.0080

Sift4G

Benign

0.093

Polyphen

0.98

Vest4

0.50

MutPred

0.27

Gain of catalytic residue at I917 (P = 0.0025)

MVP

0.12

ClinPred

0.78

GERP RS

5.5

Varity_R

0.25

gMVP

0.74

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over