chr12-46208090-G-A

Variant names:

• chr12-46208090-G-A
• rs7133522
• NM_030674.4:c.389-469C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030674.4(SLC38A1):​c.389-469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,036 control chromosomes in the GnomAD database, including 5,246 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (5246 hom., cov: 32)
• Consequence: SLC38A1 NM_030674.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

Genes affected

SLC38A1 (HGNC:13447): (solute carrier family 38 member 1) Amino acid transporters play essential roles in the uptake of nutrients, production of energy, chemical metabolism, detoxification, and neurotransmitter cycling. SLC38A1 is an important transporter of glutamine, an intermediate in the detoxification of ammonia and the production of urea. Glutamine serves as a precursor for the synaptic transmitter, glutamate (Gu et al., 2001 [PubMed 11325958]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC38A1	NM_030674.4	c.389-469C>T		intron_variant	Intron 6 of 16	ENST00000398637.10	NP_109599.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A1	ENST00000398637.10	c.389-469C>T		intron_variant	Intron 6 of 16	1	NM_030674.4	ENSP00000381634.4

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34617 AN: 151918 Hom.: 5224 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.222

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.228 AC: 34691 AN: 152036 Hom.: 5246 Cov.: 32 AF XY: 0.223 AC XY: 16595 AN XY: 74318

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.0750

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.224

Alfa AF: 0.194 Hom.: 596

Bravo AF: 0.239

Asia WGS AF: 0.136 AC: 474 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs7133522; hg19: chr12-46601873;