chr12-46201454-G-A

Position:

• chr12-46201454-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.903-256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,058 control chromosomes in the GnomAD database, including 3,320 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 (3320 hom., cov: 31)
• Consequence: SLC38A1 NM_030674.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC38A1	NM_030674.4	c.903-256C>T		intron_variant		ENST00000398637.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC38A1	ENST00000398637.10	c.903-256C>T		intron_variant		1	NM_030674.4	P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28409 AN: 151940 Hom.: 3318 Cov.: 31

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.187 AC: 28434 AN: 152058 Hom.: 3320 Cov.: 31 AF XY: 0.183 AC XY: 13622 AN XY: 74336

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0750

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.184

Alfa AF: 0.150 Hom.: 897

Bravo AF: 0.193

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.8
DANN	Benign	0.90

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: rs11183394; hg19: chr12-46595237;