chr12-46197554-G-A

Variant names:

• chr12-46197554-G-A
• rs6582621
• NM_030674.4:c.1362+166C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030674.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A1	NM_030674.4	MANE Select	c.1362+166C>T		intron	N/A	NP_109599.3
	SLC38A1	NM_001278390.1		c.1362+166C>T		intron	N/A	NP_001265319.1
	SLC38A1	NM_001077484.2		c.1362+166C>T		intron	N/A	NP_001070952.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A1	ENST00000398637.10	TSL:1 MANE Select	c.1362+166C>T		intron	N/A	ENSP00000381634.4
	SLC38A1	ENST00000552197.5	TSL:1	c.1362+166C>T		intron	N/A	ENSP00000449756.1
	SLC38A1	ENST00000439706.5	TSL:1	c.1362+166C>T		intron	N/A	ENSP00000398142.1

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

African (AFR) AF: 0.378 AC: 3460 AN: 9142

American (AMR) AF: 0.116 AC: 1389 AN: 11984

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 1675 AN: 13258

East Asian (EAS) AF: 0.109 AC: 2788 AN: 25594

South Asian (SAS) AF: 0.146 AC: 5983 AN: 41118

European-Finnish (FIN) AF: 0.110 AC: 3431 AN: 31162

Middle Eastern (MID) AF: 0.209 AC: 373 AN: 1788

European-Non Finnish (NFE) AF: 0.135 AC: 34134 AN: 252756

Other (OTH) AF: 0.154 AC: 3577 AN: 23278

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

African (AFR) AF: 0.381 AC: 15768 AN: 41408

American (AMR) AF: 0.140 AC: 2136 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3464

East Asian (EAS) AF: 0.0742 AC: 383 AN: 5162

South Asian (SAS) AF: 0.150 AC: 720 AN: 4814

European-Finnish (FIN) AF: 0.109 AC: 1148 AN: 10578

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9298 AN: 67964

Other (OTH) AF: 0.193 AC: 407 AN: 2114

Alfa AF: 0.153 Hom.: 1325

Bravo AF: 0.209

Asia WGS AF: 0.126 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.80
PhyloP100		-0.073
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: rs6582621; hg19: chr12-46591337;