chr8-37935109-C-G

Variant names:

• chr8-37935109-C-G
• NM_152413.3:c.1036G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152413.3(GOT1L1):​c.1036G>C​(p.Glu346Gln) 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 1,461,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: -0.583

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08850545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOT1L1	NM_152413.3	c.1036G>C	p.Glu346Gln	missense_variant	Exon 8 of 9	ENST00000307599.5	NP_689626.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GOT1L1	ENST00000307599.5	c.1036G>C	p.Glu346Gln	missense_variant	Exon 8 of 9	1	NM_152413.3	ENSP00000303077.4
ENSG00000285880	ENST00000647937.1	c.796G>C	p.Glu266Gln	missense_variant	Exon 2 of 2			ENSP00000497740.1
GOT1L1	ENST00000518826.3	c.367G>C	p.Glu123Gln	missense_variant	Exon 3 of 3	2		ENSP00000429558.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461398 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726980

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.5
DANN	Benign	0.42
DEOGEN2	Benign	0.11	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.74	N;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.97	N;.;.
REVEL	Benign	0.0080
Sift	Benign	0.60	T;.;.
Sift4G	Benign	0.41	T;.;.
Polyphen		0.069	B;.;.
Vest4		0.14
MutPred		0.25		Loss of sheet (P = 0.0817);.;.;
MVP		0.067
MPC		0.011
ClinPred		0.032	T
GERP RS		-1.7
Varity_R		0.050
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-37792627;