19-49431439-A-G

Position:

• chr19-49431439-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_020309.4(SLC17A7):​c.1160T>C​(p.Met387Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC17A7 NM_020309.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.17

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, SLC17A7

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A7	NM_020309.4	c.1160T>C	p.Met387Thr	missense_variant	10/12	ENST00000221485.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A7	ENST00000221485.8	c.1160T>C	p.Met387Thr	missense_variant	10/12	1	NM_020309.4	P1
SLC17A7	ENST00000600601.5	c.959T>C	p.Met320Thr	missense_variant	10/12	2
SLC17A7	ENST00000600672.5	n.1737T>C		non_coding_transcript_exon_variant	8/10	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.1160T>C (p.M387T) alteration is located in exon 10 (coding exon 10) of the SLC17A7 gene. This alteration results from a T to C substitution at nucleotide position 1160, causing the methionine (M) at amino acid position 387 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	26
DANN	Benign	0.93
DEOGEN2	Uncertain	0.77	D;.
Eigen	Benign	-0.058
Eigen_PC	Benign	0.081
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.3	D;.
REVEL	Uncertain	0.39
Sift	Benign	0.049	D;.
Sift4G	Benign	0.20	T;T
Polyphen		0.0040	B;.
Vest4		0.73
MutPred		0.63		Gain of catalytic residue at M387 (P = 0.0055);.;
MVP		0.33
MPC		1.5
ClinPred		0.96	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.53
gMVP		0.96

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-49934696;