16-58671218-C-T

Variant names:

• chr16-58671218-C-T
• rs148567685
• NM_018231.3:c.1058G>A

Variant summary

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

The NM_018231.3(SLC38A7):​c.1058G>A​(p.Arg353His) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: SLC38A7 NM_018231.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75
• 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.1058G>A	p.Arg353His	missense	Exon 10 of 12	NP_060701.1	Q9NVC3-1
	SLC38A7	NM_001369608.1		c.1058G>A	p.Arg353His	missense	Exon 10 of 12	NP_001356537.1	Q9NVC3-1
	SLC38A7	NM_001369609.1		c.1058G>A	p.Arg353His	missense	Exon 9 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.1058G>A	p.Arg353His	missense	Exon 10 of 12	ENSP00000219320.3	Q9NVC3-1
	SLC38A7	ENST00000570101.5	TSL:1	c.1058G>A	p.Arg353His	missense	Exon 9 of 11	ENSP00000454646.1	Q9NVC3-1
	SLC38A7	ENST00000564100.5	TSL:1	c.884-3731G>A		intron	N/A	ENSP00000454325.1	H3BMC5

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248708 AF XY: 0.0000148

Gnomad AFR exome AF: 0.0000632

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461550 Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6 AN XY: 727094

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000809 AC: 9 AN: 1111842

Other (OTH) AF: 0.00 AC: 0 AN: 60364

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000165 AC: 2

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	Benign	0.28
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.7
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.26
Sift	Uncertain	0.012	D
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.82
MVP		0.26
MPC		1.1
ClinPred		0.98	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.69
Mutation Taster		=18/82	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs148567685; hg19: chr16-58705122;