6-49521725-G-A

Variant names:

• chr6-49521725-G-A
• rs2127238984
• NM_001010904.2:c.394G>A

Variant summary

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

The NM_001010904.2(GLYATL3):​c.394G>A​(p.Ala132Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,112 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. 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. A132P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GLYATL3 NM_001010904.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.44
• Publications: 0 publications found

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

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=0.11547977).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010904.2. 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
	GLYATL3	NM_001010904.2	MANE Select	c.394G>A	p.Ala132Thr	missense	Exon 5 of 6	NP_001010904.1	Q5SZD4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLYATL3	ENST00000371197.9	TSL:2 MANE Select	c.394G>A	p.Ala132Thr	missense	Exon 5 of 6	ENSP00000360240.4	Q5SZD4
	GLYATL3	ENST00000545705.1	TSL:5	c.394G>A	p.Ala132Thr	missense	Exon 5 of 6	ENSP00000440029.1	F5GXQ5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399112 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690058

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35718

South Asian (SAS) AF: 0.00 AC: 0 AN: 79200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078760

Other (OTH) AF: 0.0000345 AC: 2 AN: 57994

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	18
DANN	Benign	0.88
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.081
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		2.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.076
Sift	Benign	0.51	T
Sift4G	Benign	0.67	T
Polyphen		0.0070	B
Vest4		0.30
MutPred		0.41		Gain of sheet (P = 0.0221)
MVP		0.030
ClinPred		0.21	T
GERP RS		5.9
Varity_R		0.072
gMVP		0.32
Mutation Taster		=75/25	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: rs2127238984; hg19: chr6-49489438;