8-37938728-T-C

Variant names:

• chr8-37938728-T-C
• rs61750029
• NM_152413.3:c.269A>G

Variant summary

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

The NM_152413.3(GOT1L1):​c.269A>G​(p.Lys90Arg) 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. 14/21 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)
• Consequence: GOT1L1 NM_152413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.29

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15488309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOT1L1	NM_152413.3	c.269A>G	p.Lys90Arg	missense_variant	Exon 2 of 9	ENST00000307599.5	NP_689626.2
GOT1L1	XM_005273399.4	c.269A>G	p.Lys90Arg	missense_variant	Exon 2 of 9		XP_005273456.1
GOT1L1	XM_006716285.4	c.269A>G	p.Lys90Arg	missense_variant	Exon 2 of 8		XP_006716348.1
GOT1L1	XR_949376.3	n.364A>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.269A>G	p.Lys90Arg	missense_variant	Exon 2 of 9	1	NM_152413.3	ENSP00000303077.4
ENSG00000285880	ENST00000647937.1	c.690-3513A>G		intron_variant	Intron 1 of 1			ENSP00000497740.1
GOT1L1	ENST00000524298.1	c.365A>G	p.Lys122Arg	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

Sep 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.269A>G (p.K90R) alteration is located in exon 2 (coding exon 2) of the GOT1L1 gene. This alteration results from a A to G substitution at nucleotide position 269, causing the lysine (K) at amino acid position 90 to be replaced by an arginine (R). 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	0.083
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	-0.0079
Eigen_PC	Benign	-0.078
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.075
Sift	Benign	0.27	T;T
Sift4G	Benign	0.30	T;.
Polyphen		0.99	D;.
Vest4		0.11
MutPred		0.39		Loss of ubiquitination at K90 (P = 0.0496);.;
MVP		0.12
MPC		0.013
ClinPred		0.45	T
GERP RS		2.6
Varity_R		0.082
gMVP		0.22

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: rs61750029; hg19: chr8-37796246;