19-49430690-G-T

Variant names:

• chr19-49430690-G-T
• rs7255424
• NM_020309.4:c.1512C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020309.4(SLC17A7):​c.1512C>A​(p.Ser504Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S504S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC17A7 NM_020309.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13247266).

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.1512C>A	p.Ser504Arg	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.1512C>A	p.Ser504Arg	missense	Exon 12 of 12	ENSP00000221485.2	Q9P2U7-1
	SLC17A7	ENST00000969901.1		c.1512C>A	p.Ser504Arg	missense	Exon 13 of 13	ENSP00000639960.1
	SLC17A7	ENST00000969902.1		c.1509C>A	p.Ser503Arg	missense	Exon 12 of 12	ENSP00000639961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.44
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.23
Sift	Benign	0.038	D
Sift4G	Benign	0.24	T
Polyphen		0.45	B
Vest4		0.31
MutPred		0.27		Loss of phosphorylation at S504 (P = 0.027)
MVP		0.17
MPC		0.057
ClinPred		0.75	D
GERP RS		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.42
gMVP		0.58
Mutation Taster		=40/60	disease causing

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: rs7255424; hg19: chr19-49933947;