6-49521725-G-C

Variant names:

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

Variant summary

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

The NM_001010904.2(GLYATL3):​c.394G>C​(p.Ala132Pro) 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 benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GLYATL3 NM_001010904.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.212908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLYATL3	NM_001010904.2	c.394G>C	p.Ala132Pro	missense_variant	Exon 5 of 6	ENST00000371197.9	NP_001010904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLYATL3	ENST00000371197.9	c.394G>C	p.Ala132Pro	missense_variant	Exon 5 of 6	2	NM_001010904.2	ENSP00000360240.4
GLYATL3	ENST00000545705.1	c.394G>C	p.Ala132Pro	missense_variant	Exon 5 of 6	5		ENSP00000440029.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399112 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.394G>C (p.A132P) alteration is located in exon 5 (coding exon 4) of the GLYATL3 gene. This alteration results from a G to C substitution at nucleotide position 394, causing the alanine (A) at amino acid position 132 to be replaced by a proline (P). 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	0.30
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0053	T;.
Eigen	Benign	-0.072
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.20
Sift	Benign	0.21	T;D
Sift4G	Benign	0.28	T;T
Polyphen		0.0020	B;.
Vest4		0.34
MutPred		0.54		Loss of catalytic residue at A132 (P = 0.0226);Loss of catalytic residue at A132 (P = 0.0226);
MVP		0.040
ClinPred		0.45	T
GERP RS		5.9
Varity_R		0.42
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-49489438;