rs6582621

Positions:

• chr12-46197554-G-A

Variant summary

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

The NM_030674.4(SLC38A1):​c.1362+166C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 562,060 control chromosomes in the GnomAD database, including 8,517 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 0.20 (4066 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4451 hom.)
• Consequence: SLC38A1 NM_030674.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A1	NM_030674.4	c.1362+166C>T		intron_variant		ENST00000398637.10	NP_109599.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC38A1	ENST00000398637.10	c.1362+166C>T		intron_variant		1	NM_030674.4	ENSP00000381634.4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30437 AN: 151862 Hom.: 4060 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0742

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.139 AC: 56810 AN: 410080 Hom.: 4451 Cov.: 4 AF XY: 0.138 AC XY: 30487 AN XY: 220922

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.200 AC: 30468 AN: 151980 Hom.: 4066 Cov.: 32 AF XY: 0.197 AC XY: 14610 AN XY: 74286

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0742

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.193

Alfa AF: 0.152 Hom.: 1180

Bravo AF: 0.209

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.80

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: rs6582621; hg19: chr12-46591337;