NM_020309.4:c.1214T>A

Variant names:

• chr19-49431385-A-T
• NM_020309.4:c.1214T>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020309.4(SLC17A7):​c.1214T>A​(p.Ile405Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 9.19

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A7	NM_020309.4	c.1214T>A	p.Ile405Asn	missense_variant	Exon 10 of 12	ENST00000221485.8	NP_064705.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A7	ENST00000221485.8	c.1214T>A	p.Ile405Asn	missense_variant	Exon 10 of 12	1	NM_020309.4	ENSP00000221485.2
SLC17A7	ENST00000600601.5	c.1013T>A	p.Ile338Asn	missense_variant	Exon 10 of 12	2		ENSP00000470338.1
SLC17A7	ENST00000600672.5	n.1791T>A		non_coding_transcript_exon_variant	Exon 8 of 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

Jan 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1214T>A (p.I405N) alteration is located in exon 10 (coding exon 10) of the SLC17A7 gene. This alteration results from a T to A substitution at nucleotide position 1214, causing the isoleucine (I) at amino acid position 405 to be replaced by an asparagine (N). 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	0.99
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.89	D;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Pathogenic	0.31	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.9	D;.
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.42	B;.
Vest4		0.90
MutPred		0.75		Gain of disorder (P = 0.0373);.;
MVP		0.37
MPC		3.4
ClinPred		0.99	D
GERP RS		4.0
Varity_R		0.81
gMVP		0.99

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: chr19-49934642;