Genetic Variant QTMAN:p.Met360Val (chr2-143957247-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001376312.2(QTMAN):c.1078A>G(p.Met360Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

QTMAN
NM_001376312.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Publications

0 publications found

Variant links:

Genes affected

QTMAN (HGNC:20887): (glycosyltransferase like domain containing 1) Predicted to enable glycosyltransferase activity. [provided by Alliance of Genome Resources, Apr 2022]

QTMAN Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

QTMAN links:

GTDC1-AS1 (HGNC:58227):

GTDC1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24766582).

BS2

High AC in GnomAd4 at 9 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001376312.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
QTMAN	NM_001376312.2	MANE Select	c.1078A>G	p.Met360Val	missense	Exon 9 of 12	NP_001363241.1	Q4AE62-1
QTMAN	NM_001376306.2		c.1225A>G	p.Met409Val	missense	Exon 10 of 13	NP_001363235.1
QTMAN	NM_001006636.5		c.1078A>G	p.Met360Val	missense	Exon 9 of 12	NP_001006637.1	Q4AE62-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTDC1	ENST00000682281.1	MANE Select	c.1078A>G	p.Met360Val	missense	Exon 9 of 12	ENSP00000507713.1	Q4AE62-1
GTDC1	ENST00000409214.5	TSL:1	c.1078A>G	p.Met360Val	missense	Exon 9 of 12	ENSP00000386581.1	Q4AE62-1
GTDC1	ENST00000463875.6	TSL:1	c.691A>G	p.Met231Val	missense	Exon 7 of 10	ENSP00000437964.1	Q4AE62-6

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

250248

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460236

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726458

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33388

American (AMR)

AF:

0.0000450

AC:

AN:

44402

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86008

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111232

Other (OTH)

AF:

0.0000332

AC:

AN:

60300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

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

AF:

0.0000591

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41442

American (AMR)

AF:

0.000131

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Benign

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.17

Eigen

Benign

-0.028

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.78

M_CAP

Benign

0.021

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.41

MutationAssessor

Benign

1.5

PhyloP100

3.6

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.95

REVEL

Benign

0.22

Sift

Benign

0.28

Sift4G

Benign

0.28

Polyphen

0.10

Vest4

0.44

MVP

0.46

MPC

0.079

ClinPred

0.053

GERP RS

5.9

Varity_R

0.17

gMVP

0.49

Mutation Taster

=87/13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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