NM_001376312.2:c.812G>A

Variant names:

• chr2-144007245-C-T
• rs1345731321
• NM_001376312.2:c.812G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001376312.2(QTMAN):​c.812G>A​(p.Cys271Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: QTMAN NM_001376312.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.823
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08995727).

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.812G>A	p.Cys271Tyr	missense	Exon 7 of 12	NP_001363241.1	Q4AE62-1
	QTMAN	NM_001376306.2		c.959G>A	p.Cys320Tyr	missense	Exon 8 of 13	NP_001363235.1
	QTMAN	NM_001006636.5		c.812G>A	p.Cys271Tyr	missense	Exon 7 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.812G>A	p.Cys271Tyr	missense	Exon 7 of 12	ENSP00000507713.1	Q4AE62-1
	GTDC1	ENST00000409214.5	TSL:1	c.812G>A	p.Cys271Tyr	missense	Exon 7 of 12	ENSP00000386581.1	Q4AE62-1
	GTDC1	ENST00000463875.6	TSL:1	c.425G>A	p.Cys142Tyr	missense	Exon 5 of 10	ENSP00000437964.1	Q4AE62-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.082
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	3.3
DANN	Benign	0.21
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.82
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.083
Sift	Benign	0.46	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.48		Loss of catalytic residue at P270 (P = 0.0094)
MVP		0.28
MPC		0.075
ClinPred		0.073	T
GERP RS		2.2
Varity_R		0.10
gMVP		0.30
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1345731321; hg19: chr2-144764812;