rs2241960

Positions:

• chr12-46186835-A-G
• chr12-46186835-A-T

Variant summary

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

The NM_030674.4(SLC38A1):​c.*2135T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,152 control chromosomes in the GnomAD database, including 4,488 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 0.22 (4488 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC38A1 NM_030674.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A1	NM_030674.4	c.*2135T>C		3_prime_UTR_variant	17/17	ENST00000398637.10	NP_109599.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC38A1	ENST00000398637	c.*2135T>C		3_prime_UTR_variant	17/17	1	NM_030674.4	ENSP00000381634.4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34050 AN: 152034 Hom.: 4488 Cov.: 32

Gnomad AFR AF: 0.0855

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.236

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.224 AC: 34045 AN: 152152 Hom.: 4488 Cov.: 32 AF XY: 0.222 AC XY: 16524 AN XY: 74358

Gnomad4 AFR AF: 0.0853

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.233

Alfa AF: 0.270 Hom.: 6109

Bravo AF: 0.225

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.63

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: rs2241960; hg19: chr12-46580618;