12-46206773-C-T

Position:

• chr12-46206773-C-T

Variant summary

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

The NM_030674.4(SLC38A1):​c.563+382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,032 control chromosomes in the GnomAD database, including 22,668 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 0.53 (22668 hom., cov: 32)
• Consequence: SLC38A1 NM_030674.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.478

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]

SLC38A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A1	NM_030674.4	c.563+382G>A		intron_variant		ENST00000398637.10	NP_109599.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC38A1	ENST00000398637.10	c.563+382G>A		intron_variant		1	NM_030674.4	ENSP00000381634.4

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79902 AN: 151914 Hom.: 22617 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.520

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.498

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

GnomAD4 genome AF: 0.526 AC: 80001 AN: 152032 Hom.: 22668 Cov.: 32 AF XY: 0.518 AC XY: 38479 AN XY: 74302

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.497

Alfa AF: 0.456 Hom.: 7037

Bravo AF: 0.546

Asia WGS AF: 0.403 AC: 1404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.4
DANN	Benign	0.60

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: rs1492891; hg19: chr12-46600556;