8-37934372-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152413.3(GOT1L1):​c.1187A>C​(p.Asn396Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. N396S) has been classified as Uncertain significance.

• 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: 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18172425).

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>C	p.Asn396Thr	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>C	p.Asn396Thr	missense	Exon 9 of 9	ENSP00000303077.4	Q8NHS2
	ENSG00000285880	ENST00000647937.1		c.*630A>C		3_prime_UTR	Exon 2 of 2	ENSP00000497740.1	A0A3B3IT50

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460084 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726430

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

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

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110410

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.1
DANN	Benign	0.93
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.75
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.9
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.040
Sift	Benign	0.041	D
Sift4G	Benign	0.091	T
Polyphen		0.48	P
Vest4		0.39
MutPred		0.45		Gain of catalytic residue at N396 (P = 0.0412)
MVP		0.13
MPC		0.021
ClinPred		0.52	D
GERP RS		-0.51
Varity_R		0.11
gMVP		0.18
Mutation Taster		=92/8	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;