2-143947121-C-A

Variant names:

• chr2-143947121-C-A
• rs35152029
• NM_001376312.2:c.1308G>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001376312.2(QTMAN):​c.1308G>T​(p.Pro436Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000978 in 1,613,314 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P436P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0055 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (9 hom.)
• Consequence: QTMAN NM_001376312.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.234
• 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 2-143947121-C-A is Benign according to our data. Variant chr2-143947121-C-A is described in ClinVar as Benign. ClinVar VariationId is 727232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.234 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00546 (831/152182) while in subpopulation AFR AF = 0.0195 (811/41506). AF 95% confidence interval is 0.0184. There are 10 homozygotes in GnomAd4. There are 391 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 831 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	QTMAN	NM_001376312.2	MANE Select	c.1308G>T	p.Pro436Pro	synonymous	Exon 12 of 12	NP_001363241.1	Q4AE62-1
	QTMAN	NM_001376306.2		c.1455G>T	p.Pro485Pro	synonymous	Exon 13 of 13	NP_001363235.1
	QTMAN	NM_001006636.5		c.1308G>T	p.Pro436Pro	synonymous	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.1308G>T	p.Pro436Pro	synonymous	Exon 12 of 12	ENSP00000507713.1	Q4AE62-1
	GTDC1	ENST00000409214.5	TSL:1	c.1308G>T	p.Pro436Pro	synonymous	Exon 12 of 12	ENSP00000386581.1	Q4AE62-1
	GTDC1	ENST00000463875.6	TSL:1	c.921G>T	p.Pro307Pro	synonymous	Exon 10 of 10	ENSP00000437964.1	Q4AE62-6

Frequencies

GnomAD3 genomes AF: 0.00545 AC: 828 AN: 152064 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

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: 0.0000294

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00127 AC: 318 AN: 250048 AF XY: 0.000798

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000511 AC: 747 AN: 1461132 Hom.: 9 Cov.: 29 AF XY: 0.000411 AC XY: 299 AN XY: 726956

African (AFR) AF: 0.0190 AC: 635 AN: 33446

American (AMR) AF: 0.000604 AC: 27 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5762

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111384

Other (OTH) AF: 0.00121 AC: 73 AN: 60374

GnomAD4 genome AF: 0.00546 AC: 831 AN: 152182 Hom.: 10 Cov.: 32 AF XY: 0.00525 AC XY: 391 AN XY: 74406

African (AFR) AF: 0.0195 AC: 811 AN: 41506

American (AMR) AF: 0.000915 AC: 14 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68026

Other (OTH) AF: 0.00190 AC: 4 AN: 2108

Alfa AF: 0.00190 Hom.: 6

Bravo AF: 0.00618

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	1.1
DANN	Benign	0.78
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs35152029; hg19: chr2-144704688;