16-87832984-G-T

Position:

• chr16-87832984-G-T

Variant summary

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

The NM_003486.7(SLC7A5):​c.1510C>A​(p.Pro504Thr) 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: SLC7A5 NM_003486.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.45

Genes affected

SLC7A5 (HGNC:11063): (solute carrier family 7 member 5) Enables L-leucine transmembrane transporter activity; L-tryptophan transmembrane transporter activity; and thyroid hormone transmembrane transporter activity. Involved in carboxylic acid transport; thyroid hormone transport; and xenobiotic transport. Located in cytosol; intracellular membrane-bounded organelle; and plasma membrane. Is integral component of membrane. Part of amino acid transport complex; apical plasma membrane; and microvillus membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A5	NM_003486.7	c.1510C>A	p.Pro504Thr	missense_variant	10/10	ENST00000261622.5	NP_003477.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A5	ENST00000261622.5	c.1510C>A	p.Pro504Thr	missense_variant	10/10	1	NM_003486.7	ENSP00000261622	P1
SLC7A5	ENST00000565644.5	c.712C>A	p.Pro238Thr	missense_variant	10/10	1		ENSP00000454323
SLC7A5	ENST00000563489.1	n.528C>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Aug 21, 2023

The c.1510C>A (p.P504T) alteration is located in exon 10 (coding exon 10) of the SLC7A5 gene. This alteration results from a C to A substitution at nucleotide position 1510, causing the proline (P) at amino acid position 504 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	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.85	D;T
M_CAP	Pathogenic	0.30	D
MetaRNN	Uncertain	0.64	D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.3	.;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.2	D;N
REVEL	Uncertain	0.52
Sift	Uncertain	0.024	D;T
Sift4G	Benign	0.092	T;T
Polyphen		0.99	.;D
Vest4		0.62
MutPred		0.27		.;Loss of helix (P = 0.2022);
MVP		0.86
MPC		1.9
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.51
gMVP		0.88

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: chr16-87866590;