rs376146569

Variant names:

• chr11-58709992-A-G
• rs376146569
• NM_201648.3:c.665T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-58709992-A-G
• chr11-58709992-A-T

Variant summary

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

The NM_201648.3(GLYAT):​c.665T>C​(p.Met222Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. M222K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLYAT NM_201648.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

Genes affected

GLYAT (HGNC:13734): (glycine-N-acyltransferase) The glycine-N-acyltransferase protein conjugates glycine with acyl-CoA substrates in the mitochondria. The protein is thought to be important in the detoxification of endogenous and xenobiotic acyl-CoA's. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYAT	NM_201648.3	c.665T>C	p.Met222Thr	missense_variant	Exon 6 of 6	ENST00000344743.8	NP_964011.2
GLYAT	XM_017017087.1	c.473T>C	p.Met158Thr	missense_variant	Exon 6 of 6		XP_016872576.1
GLYAT	NM_005838.4	c.*594T>C		downstream_gene_variant			NP_005829.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYAT	ENST00000344743.8	c.665T>C	p.Met222Thr	missense_variant	Exon 6 of 6	1	NM_201648.3	ENSP00000340200.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T;T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.84	T;.;.
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.4	.;D;D
REVEL	Benign	0.26
Sift	Benign	0.33	.;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.98	D;D;D
Vest4		0.24
MVP		0.50
MPC		0.13
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.30
gMVP		0.53

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: rs376146569; hg19: chr11-58477465;