rs1033697539

Variant names:

• chr8-37938753-C-T
• rs1033697539
• NM_152413.3:c.244G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-37938753-C-T
• chr8-37938753-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152413.3(GOT1L1):​c.244G>A​(p.Ala82Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000056 in 1,607,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GOT1L1 NM_152413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.518
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37794).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152413.3. 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
	GOT1L1	NM_152413.3	MANE Select	c.244G>A	p.Ala82Thr	missense	Exon 2 of 9	NP_689626.2	Q8NHS2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GOT1L1	ENST00000307599.5	TSL:1 MANE Select	c.244G>A	p.Ala82Thr	missense	Exon 2 of 9	ENSP00000303077.4	Q8NHS2
	ENSG00000285880	ENST00000647937.1		c.690-3538G>A		intron	N/A	ENSP00000497740.1	A0A3B3IT50
	GOT1L1	ENST00000524298.1	TSL:3	c.340G>A	p.Ala114Thr	missense	Exon 2 of 3	ENSP00000430453.1	E5RJX9

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455170 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2 AN XY: 723214

African (AFR) AF: 0.0000300 AC: 1 AN: 33356

American (AMR) AF: 0.0000230 AC: 1 AN: 43500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25936

East Asian (EAS) AF: 0.00 AC: 0 AN: 39510

South Asian (SAS) AF: 0.00 AC: 0 AN: 84852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109068

Other (OTH) AF: 0.0000166 AC: 1 AN: 60208

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152218 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74364

African (AFR) AF: 0.0000965 AC: 4 AN: 41450

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.093	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Benign	0.19
Eigen_PC	Benign	0.046
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.72	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.38	T
MetaSVM	Uncertain	0.35	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		0.52
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.073	T
Polyphen		0.96	D
Vest4		0.37
MVP		0.71
MPC		0.054
ClinPred		0.88	D
GERP RS		3.1
Varity_R		0.15
gMVP		0.28
Mutation Taster		=85/15	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: rs1033697539; hg19: chr8-37796271;