rs1444590

Positions:

• chr12-46205025-T-C

Variant summary

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

The NM_030674.4(SLC38A1):​c.647-435A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,112 control chromosomes in the GnomAD database, including 3,534 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 0.19 (3534 hom., cov: 32)
• Consequence: SLC38A1 NM_030674.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A1	NM_030674.4	c.647-435A>G		intron_variant		ENST00000398637.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A1	ENST00000398637.10	c.647-435A>G		intron_variant		1	NM_030674.4	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29339 AN: 151994 Hom.: 3529 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0859

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.193 AC: 29369 AN: 152112 Hom.: 3534 Cov.: 32 AF XY: 0.189 AC XY: 14069 AN XY: 74362

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.0859

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.190

Alfa AF: 0.171 Hom.: 547

Bravo AF: 0.199

Asia WGS AF: 0.129 AC: 451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.2
DANN	Benign	0.68

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: rs1444590; hg19: chr12-46598808;