14-23347964-A-T

Position:

• chr14-23347964-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016609.7(SLC22A17):​c.1204T>A​(p.Ser402Thr) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A17 NM_016609.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.29

Genes affected

SLC22A17 (HGNC:23095): (solute carrier family 22 member 17) Predicted to enable transmembrane signaling receptor activity. Predicted to be involved in siderophore transport. Is integral component of organelle membrane and integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10457951).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A17	NM_016609.7	c.1204T>A	p.Ser402Thr	missense_variant	7/10	ENST00000354772.10
SLC22A17	NM_020372.4	c.1204T>A	p.Ser402Thr	missense_variant	7/10
SLC22A17	NM_001289050.1	c.217T>A	p.Ser73Thr	missense_variant	6/9
SLC22A17	NR_110290.2	n.1088+197T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A17	ENST00000354772.10	c.1204T>A	p.Ser402Thr	missense_variant	7/10	1	NM_016609.7	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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 17, 2023

The c.871T>A (p.S291T) alteration is located in exon 6 (coding exon 6) of the SLC22A17 gene. This alteration results from a T to A substitution at nucleotide position 871, causing the serine (S) at amino acid position 291 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	Benign	0.076
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.80
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.81	T
MutationTaster	Benign	0.78	N;N;N;N
PrimateAI	Benign	0.46	T
REVEL	Benign	0.13
Polyphen		0.025, 0.072	.;B;B
Vest4		0.30
MutPred		0.42		.;Gain of glycosylation at S291 (P = 0.0542);Gain of glycosylation at S291 (P = 0.0542);
MVP		0.043
MPC		0.33
ClinPred		0.43	T
GERP RS		3.7
Varity_R		0.13
gMVP		0.16

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: chr14-23817173;