Genetic Variant NM_152413.3:c.642T>G (chr8-37936841-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152413.3(GOT1L1):c.642T>G(p.Ile214Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,632 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GOT1L1
NM_152413.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.999

Variant links:

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]

GOT1L1 links:

ENSG00000285880 (HGNC:):

ENSG00000285880 links:

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ACMG classification

Classification made for transcript

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=0.20751652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GOT1L1	NM_152413.3 link	c.642T>G	p.Ile214Met	missense_variant	Exon 6 of 9	ENST00000307599.5	NP_689626.2	Q8NHS2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GOT1L1	ENST00000307599.5 link	c.642T>G	p.Ile214Met	missense_variant	Exon 6 of 9	1	NM_152413.3	ENSP00000303077.4	Q8NHS2
ENSG00000285880	ENST00000647937.1 link	c.690-1626T>G		intron_variant	Intron 1 of 1			ENSP00000497740.1	A0A3B3IT50
GOT1L1	ENST00000518826.3 link	c.-28T>G		upstream_gene_variant		2		ENSP00000429558.2	E5RI59

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458632

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725028

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.642T>G (p.I214M) alteration is located in exon 6 (coding exon 6) of the GOT1L1 gene. This alteration results from a T to G substitution at nucleotide position 642, causing the isoleucine (I) at amino acid position 214 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.016

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.68

M_CAP

Benign

0.048

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.26

REVEL

Benign

0.27

Sift

Benign

0.10

Sift4G

Benign

0.10

Polyphen

0.14

Vest4

0.35

MutPred

0.57

Loss of catalytic residue at L219 (P = 0.2691);

MVP

0.36

MPC

0.056

ClinPred

0.23

GERP RS

-0.56

Varity_R

0.073

gMVP

0.42

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over