14-23128025-A-T

Position:

• chr14-23128025-A-T

Variant summary

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

The NM_012244.4(SLC7A8):​c.1435T>A​(p.Phe479Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC7A8 NM_012244.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

Genes affected

SLC7A8 (HGNC:11066): (solute carrier family 7 member 8) Enables several functions, including neutral amino acid transmembrane transporter activity; thyroid hormone transmembrane transporter activity; and toxin transmembrane transporter activity. Involved in L-alanine import across plasma membrane; L-leucine import across plasma membrane; and thyroid hormone transport. Located in plasma membrane. Part of basolateral plasma membrane and microvillus 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=0.20801446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A8	NM_012244.4	c.1435T>A	p.Phe479Ile	missense_variant	10/11	ENST00000316902.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A8	ENST00000316902.12	c.1435T>A	p.Phe479Ile	missense_variant	10/11	1	NM_012244.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 04, 2023

The c.1435T>A (p.F479I) alteration is located in exon 10 (coding exon 10) of the SLC7A8 gene. This alteration results from a T to A substitution at nucleotide position 1435, causing the phenylalanine (F) at amino acid position 479 to be replaced by an isoleucine (I). 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	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T;.;.;.
Eigen	Benign	-0.21
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Uncertain	-0.28	T
MutationAssessor	Uncertain	2.4	M;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.77	N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.68	T;T;T;T
Sift4G	Benign	0.54	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.32
MutPred		0.54		Gain of sheet (P = 0.0477);.;.;.;
MVP		0.87
MPC		0.20
ClinPred		0.70	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.61

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: chr14-23597234;