8-37934372-T-A

Variant names:

• chr8-37934372-T-A
• rs376778815
• NM_152413.3:c.1187A>T

Variant summary

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

The NM_152413.3(GOT1L1):​c.1187A>T​(p.Asn396Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. N396S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GOT1L1 NM_152413.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93
• 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.1187A>T	p.Asn396Ile	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.1187A>T	p.Asn396Ile	missense	Exon 9 of 9	ENSP00000303077.4	Q8NHS2
	ENSG00000285880	ENST00000647937.1		c.*630A>T		3_prime_UTR	Exon 2 of 2	ENSP00000497740.1	A0A3B3IT50

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.56
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.86	L
PhyloP100		1.9
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.093
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.029	D
Polyphen		0.93	P
Vest4		0.48
MutPred		0.47		Gain of catalytic residue at L401 (P = 0.0414)
MVP		0.32
MPC		0.044
ClinPred		0.99	D
GERP RS		-0.51
Varity_R		0.31
gMVP		0.35
Mutation Taster		=90/10	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: rs376778815; hg19: chr8-37791890;