dbSNP rs763184838: QTMAN:p.Ala435Pro (chr2-143947126-C-G) – 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_001376312.2(QTMAN):c.1303G>C(p.Ala435Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A435V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

QTMAN
NM_001376312.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.149

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: 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=0.34599286).

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.1303G>C	p.Ala435Pro	missense	Exon 12 of 12	NP_001363241.1	Q4AE62-1
QTMAN	NM_001376306.2		c.1450G>C	p.Ala484Pro	missense	Exon 13 of 13	NP_001363235.1
QTMAN	NM_001006636.5		c.1303G>C	p.Ala435Pro	missense	Exon 12 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.1303G>C	p.Ala435Pro	missense	Exon 12 of 12	ENSP00000507713.1	Q4AE62-1
GTDC1	ENST00000409214.5	TSL:1	c.1303G>C	p.Ala435Pro	missense	Exon 12 of 12	ENSP00000386581.1	Q4AE62-1
GTDC1	ENST00000463875.6	TSL:1	c.916G>C	p.Ala306Pro	missense	Exon 10 of 10	ENSP00000437964.1	Q4AE62-6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

249840

AF XY:

0.00

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:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460020

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726518

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110394

Other (OTH)

AF:

0.00

AC:

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.021

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

M_CAP

Uncertain

0.090

MetaRNN

Benign

0.35

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.4

PhyloP100

0.15

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

REVEL

Benign

0.14

Sift

Benign

0.16

Sift4G

Benign

0.18

Polyphen

0.96

Vest4

0.36

MutPred

0.49

Gain of loop (P = 0.0502)

MVP

0.60

MPC

0.16

ClinPred

0.28

GERP RS

0.47

Varity_R

0.26

gMVP

0.62

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over