2-143970683-C-G

Variant names:

• chr2-143970683-C-G
• rs778599802
• NM_001376312.2:c.955G>C

Variant summary

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

The NM_001376312.2(QTMAN):​c.955G>C​(p.Val319Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,058 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V319I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: QTMAN NM_001376312.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.59
• Publications: 0 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 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.955G>C	p.Val319Leu	missense	Exon 8 of 12	NP_001363241.1	Q4AE62-1
	QTMAN	NM_001376306.2		c.1102G>C	p.Val368Leu	missense	Exon 9 of 13	NP_001363235.1
	QTMAN	NM_001006636.5		c.955G>C	p.Val319Leu	missense	Exon 8 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.955G>C	p.Val319Leu	missense	Exon 8 of 12	ENSP00000507713.1	Q4AE62-1
	GTDC1	ENST00000409214.5	TSL:1	c.955G>C	p.Val319Leu	missense	Exon 8 of 12	ENSP00000386581.1	Q4AE62-1
	GTDC1	ENST00000463875.6	TSL:1	c.568G>C	p.Val190Leu	missense	Exon 6 of 10	ENSP00000437964.1	Q4AE62-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455058 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 724296

African (AFR) AF: 0.00 AC: 0 AN: 33344

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39658

South Asian (SAS) AF: 0.00 AC: 0 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105778

Other (OTH) AF: 0.00 AC: 0 AN: 60188

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.6
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.46
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.010	D
Polyphen		0.90	P
Vest4		0.54
MutPred		0.61		Gain of sheet (P = 0.1451)
MVP		0.37
MPC		0.18
ClinPred		0.93	D
GERP RS		3.1
Varity_R		0.24
gMVP		0.61
Mutation Taster		=81/19	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: rs778599802; hg19: chr2-144728250;