chr11-58834499-T-A

Variant names:

• chr11-58834499-T-A
• rs773639109
• NM_145016.4:c.815A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145016.4(GLYATL2):​c.815A>T​(p.Asn272Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000366 in 1,613,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: GLYATL2 NM_145016.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.77

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.093941).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL2	NM_145016.4	c.815A>T	p.Asn272Ile	missense_variant	Exon 6 of 6	ENST00000287275.6	NP_659453.3
GLYATL2	XM_017017337.3	c.815A>T	p.Asn272Ile	missense_variant	Exon 7 of 7		XP_016872826.1
GLYATL2	XM_017017338.3	c.815A>T	p.Asn272Ile	missense_variant	Exon 6 of 6		XP_016872827.1
GLYATL2	XM_047426545.1	c.692A>T	p.Asn231Ile	missense_variant	Exon 5 of 5		XP_047282501.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYATL2	ENST00000287275.6	c.815A>T	p.Asn272Ile	missense_variant	Exon 6 of 6	1	NM_145016.4	ENSP00000287275.1
GLYATL2	ENST00000532258.1	c.815A>T	p.Asn272Ile	missense_variant	Exon 7 of 7	1		ENSP00000434277.1
GLYATL2	ENST00000533636.1	n.*231A>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 248928 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135050

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461206 Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28 AN XY: 726892

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000672

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.0000663

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74372

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000340

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.815A>T (p.N272I) alteration is located in exon 6 (coding exon 5) of the GLYATL2 gene. This alteration results from a A to T substitution at nucleotide position 815, causing the asparagine (N) at amino acid position 272 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.013
DANN	Benign	0.52
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.26	.;T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.094	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.019
Sift	Benign	0.17	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.0010	B;B
Vest4		0.21
MutPred		0.34		Loss of disorder (P = 0.0428);Loss of disorder (P = 0.0428);
MVP		0.23
MPC		0.018
ClinPred		0.031	T
GERP RS		-7.5
Varity_R		0.097
gMVP		0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs773639109; hg19: chr11-58601972;