NM_020309.4:c.1513G>A

Variant names:

• chr19-49430689-C-T
• rs376101582
• NM_020309.4:c.1513G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_020309.4(SLC17A7):​c.1513G>A​(p.Glu505Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC17A7 NM_020309.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.01
• Publications: 0 publications found

Genes affected

SLC17A7 (HGNC:16704): (solute carrier family 17 member 7) The protein encoded by this gene is a vesicle-bound, sodium-dependent phosphate transporter that is specifically expressed in the neuron-rich regions of the brain. It is preferentially associated with the membranes of synaptic vesicles and functions in glutamate transport. The protein shares 82% identity with the differentiation-associated Na-dependent inorganic phosphate cotransporter and they appear to form a distinct class within the Na+/Pi cotransporter family. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17327982).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020309.4. 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
	SLC17A7	NM_020309.4	MANE Select	c.1513G>A	p.Glu505Lys	missense	Exon 12 of 12	NP_064705.1	Q9P2U7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A7	ENST00000221485.8	TSL:1 MANE Select	c.1513G>A	p.Glu505Lys	missense	Exon 12 of 12	ENSP00000221485.2	Q9P2U7-1
	SLC17A7	ENST00000969901.1		c.1513G>A	p.Glu505Lys	missense	Exon 13 of 13	ENSP00000639960.1
	SLC17A7	ENST00000969902.1		c.1510G>A	p.Glu504Lys	missense	Exon 12 of 12	ENSP00000639961.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152164 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461878 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74322

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

African (AFR) AF: 0.0000241 AC: 1 AN: 41420

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

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: 0.00 AC: 0 AN: 68030

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 = 0.0136242), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

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	0.26
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D
Eigen	Benign	0.073
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.0
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.12
Sift	Benign	0.049	D
Sift4G	Benign	0.066	T
Polyphen		0.28	B
Vest4		0.28
MutPred		0.35		Gain of ubiquitination at E505 (P = 0.0037)
MVP		0.082
MPC		0.052
ClinPred		0.85	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.28
gMVP		0.50
Mutation Taster		=69/31	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: rs376101582; hg19: chr19-49933946;