NM_018976.5:c.474C>T

Variant names:

• chr12-46367083-G-A
• rs36022751
• NM_018976.5:c.474C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_018976.5(SLC38A2):​c.474C>T​(p.Asn158Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00813 in 1,613,734 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (76 hom.)
• Consequence: SLC38A2 NM_018976.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.07
• Publications: 1 publications found

Genes affected

SLC38A2 (HGNC:13448): (solute carrier family 38 member 2) Enables neutral amino acid:sodium symporter activity. Involved in several processes, including amino acid transport; cellular response to arsenite(3-); and positive regulation of RNA splicing. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 12-46367083-G-A is Benign according to our data. Variant chr12-46367083-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 791632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.07 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018976.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A2	NM_018976.5	MANE Select	c.474C>T	p.Asn158Asn	synonymous	Exon 6 of 16	NP_061849.2
	SLC38A2	NM_001307936.2		c.174C>T	p.Asn58Asn	synonymous	Exon 5 of 15	NP_001294865.1	Q96QD8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A2	ENST00000256689.10	TSL:1 MANE Select	c.474C>T	p.Asn158Asn	synonymous	Exon 6 of 16	ENSP00000256689.5	Q96QD8-1
	SLC38A2	ENST00000612232.1	TSL:1	c.174C>T	p.Asn58Asn	synonymous	Exon 3 of 13	ENSP00000482873.1	Q96QD8-2
	SLC38A2	ENST00000901221.1		c.474C>T	p.Asn158Asn	synonymous	Exon 5 of 15	ENSP00000571280.1

Frequencies

GnomAD3 genomes AF: 0.00598 AC: 910 AN: 152184 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00176

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00958

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00611 AC: 1535 AN: 251096 AF XY: 0.00629

Gnomad AFR exome AF: 0.00118

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.0163

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00394

Gnomad NFE exome AF: 0.00907

Gnomad OTH exome AF: 0.00768

GnomAD4 exome AF: 0.00836 AC: 12211 AN: 1461432 Hom.: 76 Cov.: 31 AF XY: 0.00830 AC XY: 6036 AN XY: 727052

African (AFR) AF: 0.000986 AC: 33 AN: 33474

American (AMR) AF: 0.00329 AC: 147 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 461 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00263 AC: 227 AN: 86238

European-Finnish (FIN) AF: 0.00562 AC: 300 AN: 53348

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.00940 AC: 10449 AN: 1111688

Other (OTH) AF: 0.00967 AC: 584 AN: 60384

GnomAD4 genome AF: 0.00597 AC: 910 AN: 152302 Hom.: 5 Cov.: 32 AF XY: 0.00584 AC XY: 435 AN XY: 74478

African (AFR) AF: 0.00176 AC: 73 AN: 41550

American (AMR) AF: 0.00483 AC: 74 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00290 AC: 14 AN: 4832

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00958 AC: 652 AN: 68028

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00877 Hom.: 6

Bravo AF: 0.00560

Asia WGS AF: 0.00202 AC: 8 AN: 3478

EpiCase AF: 0.00976

EpiControl AF: 0.00931

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	9.3
DANN	Benign	0.73
PhyloP100		3.1
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Mutation Taster		=100/0	polymorphism

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: rs36022751; hg19: chr12-46760866; COSMIC: COSV56744336; COSMIC: COSV56744336;