11-58834553-A-G

Variant names:

• chr11-58834553-A-G
• rs909496704
• NM_145016.4:c.761T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145016.4(GLYATL2):​c.761T>C​(p.Ile254Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. I254N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GLYATL2 NM_145016.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.99
• Publications: 0 publications found

Genes affected

GLYATL2 (HGNC:24178): (glycine-N-acyltransferase like 2) Enables glycine N-acyltransferase activity. Involved in long-chain fatty acid catabolic process; medium-chain fatty acid catabolic process; and monounsaturated fatty acid catabolic process. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000289621 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35817015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145016.4. 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
	GLYATL2	NM_145016.4	MANE Select	c.761T>C	p.Ile254Thr	missense	Exon 6 of 6	NP_659453.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLYATL2	ENST00000287275.6	TSL:1 MANE Select	c.761T>C	p.Ile254Thr	missense	Exon 6 of 6	ENSP00000287275.1	Q8WU03
	GLYATL2	ENST00000532258.1	TSL:1	c.761T>C	p.Ile254Thr	missense	Exon 7 of 7	ENSP00000434277.1	Q8WU03
	ENSG00000289621	ENST00000529451.2	TSL:2	n.424-43705A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461418 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727024

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111664

Other (OTH) AF: 0.0000166 AC: 1 AN: 60374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.90
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		2.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.059
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.013	D
Polyphen		0.058	B
Vest4		0.18
MutPred		0.70		Gain of disorder (P = 0.026)
MVP		0.29
MPC		0.055
ClinPred		0.19	T
GERP RS		3.6
Varity_R		0.20
gMVP		0.28
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: rs909496704; hg19: chr11-58602026;