rs766948706

Variant names:

• chr8-37938843-C-G
• rs766948706
• NM_152413.3:c.154G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-37938843-C-G
• chr8-37938843-C-T

Variant summary

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

The NM_152413.3(GOT1L1):​c.154G>C​(p.Val52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: GOT1L1 NM_152413.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOT1L1	NM_152413.3	c.154G>C	p.Val52Leu	missense_variant	Exon 2 of 9	ENST00000307599.5	NP_689626.2
GOT1L1	XM_005273399.4	c.154G>C	p.Val52Leu	missense_variant	Exon 2 of 9		XP_005273456.1
GOT1L1	XM_006716285.4	c.154G>C	p.Val52Leu	missense_variant	Exon 2 of 8		XP_006716348.1
GOT1L1	XR_949376.3	n.249G>C		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.154G>C	p.Val52Leu	missense_variant	Exon 2 of 9	1	NM_152413.3	ENSP00000303077.4
ENSG00000285880	ENST00000647937.1	c.690-3628G>C		intron_variant	Intron 1 of 1			ENSP00000497740.1
GOT1L1	ENST00000524298.1	c.250G>C	p.Val84Leu	missense_variant	Exon 2 of 3	3		ENSP00000430453.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.72	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Pathogenic	3.2	M;.
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		0.75	P;.
Vest4		0.56
MutPred		0.76		Gain of helix (P = 0.1736);.;
MVP		0.57
MPC		0.067
ClinPred		0.83	D
GERP RS		3.8
Varity_R		0.39
gMVP		0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs766948706; hg19: chr8-37796361;