NM_001010904.2:c.599C>T

Variant names:

• chr6-49526646-C-T
• rs1389168434
• NM_001010904.2:c.599C>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001010904.2(GLYATL3):​c.599C>T​(p.Pro200Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. P200Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLYATL3 NM_001010904.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95

Genes affected

GLYATL3 (HGNC:21349): (glycine-N-acyltransferase like 3) Predicted to enable glycine N-acyltransferase activity. Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.904

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL3	NM_001010904.2	c.599C>T	p.Pro200Leu	missense_variant	Exon 6 of 6	ENST00000371197.9	NP_001010904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYATL3	ENST00000371197.9	c.599C>T	p.Pro200Leu	missense_variant	Exon 6 of 6	2	NM_001010904.2	ENSP00000360240.4
GLYATL3	ENST00000545705.1	c.*131C>T		downstream_gene_variant		5		ENSP00000440029.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.019	T
MetaRNN	Pathogenic	0.90	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.30	N
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-7.9	D
REVEL	Uncertain	0.36
Sift	Benign	0.13	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.77		Gain of sheet (P = 0.039);
MVP		0.12
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.42
gMVP		0.86

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: rs1389168434; hg19: chr6-49494359;