NM_152413.3:c.1142G>A

Variant names:

• chr8-37934417-C-T
• rs1455842170
• NM_152413.3:c.1142G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152413.3(GOT1L1):​c.1142G>A​(p.Ser381Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,562 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S381T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GOT1L1 NM_152413.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.1142G>A	p.Ser381Asn	missense	Exon 9 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.1142G>A	p.Ser381Asn	missense	Exon 9 of 9	ENSP00000303077.4	Q8NHS2
	ENSG00000285880	ENST00000647937.1		c.*585G>A		3_prime_UTR	Exon 2 of 2	ENSP00000497740.1	A0A3B3IT50

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461562 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727064

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111732

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Benign	-0.0032	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Uncertain	0.50	D
Eigen	Benign	-0.078
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.7	L
PhyloP100		3.6
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.11	T
Polyphen		0.80	P
Vest4		0.37
MutPred		0.69		Loss of sheet (P = 0.0037)
MVP		0.53
MPC		0.018
ClinPred		0.79	D
GERP RS		3.5
Varity_R		0.19
gMVP		0.50
Mutation Taster		=94/6	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: rs1455842170; hg19: chr8-37791935;