16-58672199-C-T

Variant names:

• chr16-58672199-C-T
• rs1469310878
• NM_018231.3:c.928G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018231.3(SLC38A7):​c.928G>A​(p.Val310Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000887 in 1,578,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000084 (0 hom.)
• Consequence: SLC38A7 NM_018231.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71
• Publications: 2 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.776

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.928G>A	p.Val310Met	missense	Exon 9 of 12	NP_060701.1	Q9NVC3-1
	SLC38A7	NM_001369608.1		c.928G>A	p.Val310Met	missense	Exon 9 of 12	NP_001356537.1	Q9NVC3-1
	SLC38A7	NM_001369609.1		c.928G>A	p.Val310Met	missense	Exon 8 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.928G>A	p.Val310Met	missense	Exon 9 of 12	ENSP00000219320.3	Q9NVC3-1
	SLC38A7	ENST00000570101.5	TSL:1	c.928G>A	p.Val310Met	missense	Exon 8 of 11	ENSP00000454646.1	Q9NVC3-1
	SLC38A7	ENST00000564100.5	TSL:1	c.883+3741G>A		intron	N/A	ENSP00000454325.1	H3BMC5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152032 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000518 AC: 1 AN: 193016 AF XY: 0.00000970

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000841 AC: 12 AN: 1426142 Hom.: 0 Cov.: 31 AF XY: 0.0000113 AC XY: 8 AN XY: 705942

African (AFR) AF: 0.00 AC: 0 AN: 32752

American (AMR) AF: 0.0000255 AC: 1 AN: 39160

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25410

East Asian (EAS) AF: 0.00 AC: 0 AN: 37866

South Asian (SAS) AF: 0.0000864 AC: 7 AN: 81060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50972

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5730

European-Non Finnish (NFE) AF: 0.00000366 AC: 4 AN: 1094128

Other (OTH) AF: 0.00 AC: 0 AN: 59064

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152032 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74256

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000242 AC: 1 AN: 41390

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68006

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

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	0.88
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.7
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.4	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.81
MutPred		0.75		Gain of disorder (P = 0.0975)
MVP		0.60
MPC		0.89
ClinPred		0.81	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
gMVP		0.73
Mutation Taster		=65/35	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: rs1469310878; hg19: chr16-58706103; COSMIC: COSV54702140; COSMIC: COSV54702140;