NM_018231.3:c.847G>A

Variant names:

• chr16-58675976-C-T
• NM_018231.3:c.847G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018231.3(SLC38A7):​c.847G>A​(p.Ala283Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,300 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SLC38A7 NM_018231.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.27
• Publications: 0 publications found

Genes affected

SLC38A7 (HGNC:25582): (solute carrier family 38 member 7) Predicted to enable L-amino acid transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and sodium ion transport. Predicted to be located in axon and neuronal cell body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018231.3. 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
	SLC38A7	NM_018231.3	MANE Select	c.847G>A	p.Ala283Thr	missense	Exon 8 of 12	NP_060701.1	Q9NVC3-1
	SLC38A7	NM_001369608.1		c.847G>A	p.Ala283Thr	missense	Exon 8 of 12	NP_001356537.1	Q9NVC3-1
	SLC38A7	NM_001369609.1		c.847G>A	p.Ala283Thr	missense	Exon 7 of 11	NP_001356538.1	Q9NVC3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A7	ENST00000219320.9	TSL:1 MANE Select	c.847G>A	p.Ala283Thr	missense	Exon 8 of 12	ENSP00000219320.3	Q9NVC3-1
	SLC38A7	ENST00000570101.5	TSL:1	c.847G>A	p.Ala283Thr	missense	Exon 7 of 11	ENSP00000454646.1	Q9NVC3-1
	SLC38A7	ENST00000564100.5	TSL:1	c.847G>A	p.Ala283Thr	missense	Exon 7 of 8	ENSP00000454325.1	H3BMC5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461300 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726894

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111804

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.011	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.3
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.22
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.031	D
Polyphen		0.96	P
Vest4		0.54
MutPred		0.72		Loss of stability (P = 0.1463)
MVP		0.57
MPC		0.71
ClinPred		0.87	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.79
Mutation Taster		=47/53	disease causing

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

hg19: chr16-58709880;