NM_001389712.2:c.404C>T

Variant names:

• chr11-58955266-C-T
• rs757759933
• NM_001389712.2:c.404C>T

Variant summary

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

The NM_001389712.2(GLYATL1):​c.404C>T​(p.Thr135Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 1,461,754 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: GLYATL1 NM_001389712.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.670
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10000372).

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.404C>T	p.Thr135Met	missense	Exon 6 of 7	NP_001376641.1	Q969I3-1
	GLYATL1	NM_080661.6		c.497C>T	p.Thr166Met	missense	Exon 6 of 7	NP_542392.2
	GLYATL1	NM_001220494.4		c.404C>T	p.Thr135Met	missense	Exon 7 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.404C>T	p.Thr135Met	missense	Exon 6 of 7	ENSP00000436116.2	Q969I3-1
	GLYATL1	ENST00000317391.8	TSL:1	c.404C>T	p.Thr135Met	missense	Exon 7 of 8	ENSP00000322223.4	Q969I3-1
	GLYATL1	ENST00000612196.1	TSL:1	c.404C>T	p.Thr135Met	missense	Exon 4 of 5	ENSP00000479741.1	Q969I3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000318 AC: 8 AN: 251450 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: 0.0000528

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000431 AC: 63 AN: 1461754 Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39 AN XY: 727184

African (AFR) AF: 0.0000597 AC: 2 AN: 33478

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86250

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

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

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111892

Other (OTH) AF: 0.0000166 AC: 1 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000264

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.000178

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	-0.39	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.1
DANN	Benign	0.53
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.33	N
PhyloP100		-0.67
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.0070
Sift	Benign	0.29	T
Sift4G	Benign	0.12	T
Polyphen		0.24	B
Vest4		0.23
MutPred		0.39		Loss of sheet (P = 0.007)
MVP		0.22
MPC		0.084
ClinPred		0.019	T
GERP RS		-0.48
Varity_R		0.024
gMVP		0.22
Mutation Taster		=98/2	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: rs757759933; hg19: chr11-58722739; COSMIC: COSV55610381; COSMIC: COSV55610381;