chr12-46206773-C-T

Variant names:

• chr12-46206773-C-T
• rs1492891
• NM_030674.4:c.563+382G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC38A1	NM_030674.4	c.563+382G>A		intron_variant	Intron 8 of 16	ENST00000398637.10	NP_109599.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC38A1	ENST00000398637.10	c.563+382G>A		intron_variant	Intron 8 of 16	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

African (AFR) AF: 0.756 AC: 31359 AN: 41480

American (AMR) AF: 0.520 AC: 7944 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1435 AN: 3472

East Asian (EAS) AF: 0.419 AC: 2167 AN: 5174

South Asian (SAS) AF: 0.356 AC: 1720 AN: 4830

European-Finnish (FIN) AF: 0.390 AC: 4119 AN: 10558

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29724 AN: 67950

Other (OTH) AF: 0.497 AC: 1042 AN: 2098

Alfa AF: 0.458 Hom.: 8041

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
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs1492891; hg19: chr12-46600556;