rs145455204

Variant names:

• chr19-49430671-C-A
• rs145455204
• NM_020309.4:c.1531G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-49430671-C-A
• chr19-49430671-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020309.4(SLC17A7):​c.1531G>T​(p.Val511Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,614,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SLC17A7 NM_020309.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24
• Publications: 4 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032333225).
• BS2: High AC in GnomAd4 at 26 AD gene.

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.1531G>T	p.Val511Phe	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.1531G>T	p.Val511Phe	missense	Exon 12 of 12	ENSP00000221485.2	Q9P2U7-1
	SLC17A7	ENST00000969901.1		c.1531G>T	p.Val511Phe	missense	Exon 13 of 13	ENSP00000639960.1
	SLC17A7	ENST00000969902.1		c.1528G>T	p.Val510Phe	missense	Exon 12 of 12	ENSP00000639961.1

Frequencies

GnomAD3 genomes AF: 0.000171 AC: 26 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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

GnomAD2 exomes AF: 0.0000599 AC: 15 AN: 250552 AF XY: 0.0000590

Gnomad AFR exome AF: 0.000873

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: 0.000164

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461872 Hom.: 0 Cov.: 33 AF XY: 0.0000110 AC XY: 8 AN XY: 727246

African (AFR) AF: 0.000568 AC: 19 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 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: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.000171 AC: 26 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74448

African (AFR) AF: 0.000601 AC: 25 AN: 41564

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.0000447 Hom.: 0

Bravo AF: 0.000196

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000741 AC: 9

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	0.17
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Benign	0.093
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N
PhyloP100		2.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.60	T
Polyphen		0.65	P
Vest4		0.20
MVP		0.068
MPC		0.084
ClinPred		0.051	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.14
gMVP		0.35
Mutation Taster		=74/26	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: rs145455204; hg19: chr19-49933928; COSMIC: COSV55548819; COSMIC: COSV55548819;