NM_001389712.2:c.139G>A

Variant names:

• chr11-58947918-G-A
• rs777421609
• NM_001389712.2:c.139G>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001389712.2(GLYATL1):​c.139G>A​(p.Asp47Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: GLYATL1 NM_001389712.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.98
• Publications: 0 publications found

Genes affected

GLYATL1 (HGNC:30519): (glycine-N-acyltransferase like 1) Enables glutamine N-acyltransferase activity. Involved in glutamine metabolic process. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

GLYATL1-AS1 (HGNC:58086):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001389712.2. 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
	GLYATL1	NM_001389712.2	MANE Select	c.139G>A	p.Asp47Asn	missense	Exon 4 of 7	NP_001376641.1	Q969I3-1
	GLYATL1	NM_080661.6		c.232G>A	p.Asp78Asn	missense	Exon 4 of 7	NP_542392.2
	GLYATL1	NM_001220494.4		c.139G>A	p.Asp47Asn	missense	Exon 5 of 8	NP_001207423.1	Q969I3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLYATL1	ENST00000532726.6	TSL:3 MANE Select	c.139G>A	p.Asp47Asn	missense	Exon 4 of 7	ENSP00000436116.2	Q969I3-1
	GLYATL1	ENST00000317391.8	TSL:1	c.139G>A	p.Asp47Asn	missense	Exon 5 of 8	ENSP00000322223.4	Q969I3-1
	GLYATL1	ENST00000612196.1	TSL:1	c.139G>A	p.Asp47Asn	missense	Exon 2 of 5	ENSP00000479741.1	Q969I3-1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152150 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000437 AC: 11 AN: 251458 AF XY: 0.0000368

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: 0.0000967

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000342 AC: 50 AN: 1461794 Hom.: 0 Cov.: 30 AF XY: 0.0000426 AC XY: 31 AN XY: 727212

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111960

Other (OTH) AF: 0.0000166 AC: 1 AN: 60388

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152150 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41406

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000966 Hom.: 0

Bravo AF: 0.0000604

ExAC AF: 0.0000576 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	Uncertain	0.42
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.098
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.0074	T
MetaRNN	Pathogenic	0.96	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.0
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.36
MutPred		0.93		Loss of sheet (P = 0.0126)
MVP		0.58
MPC		0.37
ClinPred		0.89	D
GERP RS		3.4
Varity_R		0.74
gMVP		0.62
Mutation Taster		=96/4	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: rs777421609; hg19: chr11-58715391;