14-23129663-G-T

Position:

• chr14-23129663-G-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.1250C>A​(p.Pro417His) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC7A8 NM_012244.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71

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=0.19687366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A8	NM_012244.4	c.1250C>A	p.Pro417His	missense_variant	9/11	ENST00000316902.12	NP_036376.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A8	ENST00000316902.12	c.1250C>A	p.Pro417His	missense_variant	9/11	1	NM_012244.4	ENSP00000320378	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

May 29, 2024

The c.1250C>A (p.P417H) alteration is located in exon 9 (coding exon 9) of the SLC7A8 gene. This alteration results from a C to A substitution at nucleotide position 1250, causing the proline (P) at amino acid position 417 to be replaced by a histidine (H). 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	0.075
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Uncertain	0.55	D;.;.;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.20	T;T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Benign	-0.080	N;.;.;.
MutationTaster	Benign	0.96	D;D;D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.25	N;N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.67	T;T;T;T
Sift4G	Benign	0.64	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.12
MutPred		0.49		Gain of MoRF binding (P = 0.0505);.;.;.;
MVP		0.93
MPC		0.17
ClinPred		0.49	T
GERP RS		4.0
Varity_R		0.092
gMVP		0.79

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: chr14-23598872;