chr2-143947132-C-T

Variant names:

• chr2-143947132-C-T
• rs763999077
• NM_001376312.2:c.1297G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001376312.2(QTMAN):​c.1297G>A​(p.Glu433Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,864 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: 0.0000021 (0 hom.)
• Consequence: QTMAN NM_001376312.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19
• Publications: 1 publications found

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

GTDC1-AS1 (HGNC:58227):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QTMAN	NM_001376312.2	MANE Select	c.1297G>A	p.Glu433Lys	missense	Exon 12 of 12	NP_001363241.1	Q4AE62-1
	QTMAN	NM_001376306.2		c.1444G>A	p.Glu482Lys	missense	Exon 13 of 13	NP_001363235.1
	QTMAN	NM_001006636.5		c.1297G>A	p.Glu433Lys	missense	Exon 12 of 12	NP_001006637.1	Q4AE62-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTDC1	ENST00000682281.1	MANE Select	c.1297G>A	p.Glu433Lys	missense	Exon 12 of 12	ENSP00000507713.1	Q4AE62-1
	GTDC1	ENST00000409214.5	TSL:1	c.1297G>A	p.Glu433Lys	missense	Exon 12 of 12	ENSP00000386581.1	Q4AE62-1
	GTDC1	ENST00000463875.6	TSL:1	c.910G>A	p.Glu304Lys	missense	Exon 10 of 10	ENSP00000437964.1	Q4AE62-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249794 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458864 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726042

African (AFR) AF: 0.00 AC: 0 AN: 33392

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109312

Other (OTH) AF: 0.0000498 AC: 3 AN: 60296

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.045
Sift	Benign	0.092	T
Sift4G	Benign	0.16	T
Polyphen		0.0080	B
Vest4		0.26
MutPred		0.43		Gain of MoRF binding (P = 0.003)
MVP		0.51
MPC		0.044
ClinPred		0.26	T
GERP RS		4.0
Varity_R		0.17
gMVP		0.39
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.23		Position offset: 3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs763999077; hg19: chr2-144704699;