16-58675958-C-A

Variant names:

• chr16-58675958-C-A
• rs868782902
• NM_018231.3:c.865G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018231.3(SLC38A7):​c.865G>T​(p.Ala289Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A289T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC38A7 NM_018231.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.12
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28302234).

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.865G>T	p.Ala289Ser	missense	Exon 8 of 12	NP_060701.1	Q9NVC3-1
	SLC38A7	NM_001369608.1		c.865G>T	p.Ala289Ser	missense	Exon 8 of 12	NP_001356537.1	Q9NVC3-1
	SLC38A7	NM_001369609.1		c.865G>T	p.Ala289Ser	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.865G>T	p.Ala289Ser	missense	Exon 8 of 12	ENSP00000219320.3	Q9NVC3-1
	SLC38A7	ENST00000570101.5	TSL:1	c.865G>T	p.Ala289Ser	missense	Exon 7 of 11	ENSP00000454646.1	Q9NVC3-1
	SLC38A7	ENST00000564100.5	TSL:1	c.865G>T	p.Ala289Ser	missense	Exon 7 of 8	ENSP00000454325.1	H3BMC5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460114 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726218

African (AFR) AF: 0.00 AC: 0 AN: 33430

American (AMR) AF: 0.00 AC: 0 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 85888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111282

Other (OTH) AF: 0.00 AC: 0 AN: 60326

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.10
Sift	Benign	0.047	D
Sift4G	Benign	0.069	T
Polyphen		0.58	P
Vest4		0.29
MutPred		0.64		Gain of helix (P = 0.2294)
MVP		0.29
MPC		0.47
ClinPred		0.85	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.077
gMVP		0.35
Mutation Taster		=90/10	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: rs868782902; hg19: chr16-58709862;