rs376778815

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-37934372-T-C
• chr8-37934372-T-A
• chr8-37934372-T-G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_152413.3(GOT1L1):​c.1187A>G​(p.Asn396Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,612,406 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000039 (2 hom.)
• Consequence: GOT1L1 NM_152413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024758011).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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>G	p.Asn396Ser	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>G	p.Asn396Ser	missense	Exon 9 of 9	ENSP00000303077.4	Q8NHS2
	ENSG00000285880	ENST00000647937.1		c.*630A>G		3_prime_UTR	Exon 2 of 2	ENSP00000497740.1	A0A3B3IT50

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000108 AC: 27 AN: 249246 AF XY: 0.000104

Gnomad AFR exome AF: 0.000775

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1460084 Hom.: 2 Cov.: 30 AF XY: 0.0000496 AC XY: 36 AN XY: 726430

African (AFR) AF: 0.000508 AC: 17 AN: 33448

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

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

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39688

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86220

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

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00000811 AC: 9 AN: 1110410

Other (OTH) AF: 0.0000166 AC: 1 AN: 60316

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152322 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74496

African (AFR) AF: 0.000385 AC: 16 AN: 41570

American (AMR) AF: 0.000131 AC: 2 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000197 Hom.: 0

Bravo AF: 0.000200

ESP6500AA AF: 0.000791 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000166 AC: 20

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.3
DANN	Benign	0.87
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.39	N
PhyloP100		1.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.033
Sift	Benign	0.069	T
Sift4G	Benign	0.19	T
Polyphen		0.024	B
Vest4		0.21
MVP		0.18
MPC		0.011
ClinPred		0.011	T
GERP RS		-0.51
Varity_R		0.056
gMVP		0.13
Mutation Taster		=97/3	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;