8-37938828-G-C

Variant names:

• chr8-37938828-G-C
• NM_152413.3:c.169C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_152413.3(GOT1L1):​c.169C>G​(p.Arg57Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOT1L1 NM_152413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

Genes affected

GOT1L1 (HGNC:28487): (glutamic-oxaloacetic transaminase 1 like 1) Predicted to enable L-aspartate:2-oxoglutarate aminotransferase activity. Predicted to be involved in aspartate biosynthetic process. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285880 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOT1L1	NM_152413.3	c.169C>G	p.Arg57Gly	missense_variant	Exon 2 of 9	ENST00000307599.5	NP_689626.2
GOT1L1	XM_005273399.4	c.169C>G	p.Arg57Gly	missense_variant	Exon 2 of 9		XP_005273456.1
GOT1L1	XM_006716285.4	c.169C>G	p.Arg57Gly	missense_variant	Exon 2 of 8		XP_006716348.1
GOT1L1	XR_949376.3	n.264C>G		non_coding_transcript_exon_variant	Exon 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOT1L1	ENST00000307599.5	c.169C>G	p.Arg57Gly	missense_variant	Exon 2 of 9	1	NM_152413.3	ENSP00000303077.4
ENSG00000285880	ENST00000647937.1	c.690-3613C>G		intron_variant	Intron 1 of 1			ENSP00000497740.1
GOT1L1	ENST00000524298.1	c.265C>G	p.Arg89Gly	missense_variant	Exon 2 of 3	3		ENSP00000430453.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.169C>G (p.R57G) alteration is located in exon 2 (coding exon 2) of the GOT1L1 gene. This alteration results from a C to G substitution at nucleotide position 169, causing the arginine (R) at amino acid position 57 to be replaced by a glycine (G). 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	Uncertain	0.45
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.57	D;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.72	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Uncertain	0.032	D
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.11	T;.
Polyphen		0.96	D;.
Vest4		0.49
MutPred		0.72		Loss of stability (P = 0.114);.;
MVP		0.57
MPC		0.055
ClinPred		0.96	D
GERP RS		3.8
Varity_R		0.25
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-37796346;