NM_012244.4:c.1114T>G

Variant names:

• chr14-23129799-A-C
• rs752410256
• NM_012244.4:c.1114T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_012244.4(SLC7A8):​c.1114T>G​(p.Cys372Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,696 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (1 hom.)
• Consequence: SLC7A8 NM_012244.4 missense, splice_region
• Scores: Splicing: ADA: 0.0002496
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.43
• Publications: 0 publications found

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]

ENSG00000295888 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.828

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012244.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A8	NM_012244.4	MANE Select	c.1114T>G	p.Cys372Gly	missense splice_region	Exon 9 of 11	NP_036376.2
	SLC7A8	NM_001267036.1		c.799T>G	p.Cys267Gly	missense splice_region	Exon 7 of 9	NP_001253965.1	Q9UHI5-4
	SLC7A8	NM_182728.3		c.505T>G	p.Cys169Gly	missense splice_region	Exon 7 of 9	NP_877392.1	Q9UHI5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A8	ENST00000316902.12	TSL:1 MANE Select	c.1114T>G	p.Cys372Gly	missense splice_region	Exon 9 of 11	ENSP00000320378.7	Q9UHI5-1
	SLC7A8	ENST00000453702.5	TSL:1	c.505T>G	p.Cys169Gly	missense splice_region	Exon 7 of 9	ENSP00000391577.1	Q9UHI5-2
	SLC7A8	ENST00000469263.5	TSL:1	c.789-2456T>G		intron	N/A	ENSP00000435114.1	E9PLV9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000199 AC: 5 AN: 250836 AF XY: 0.0000369

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 23 AN: 1461696 Hom.: 1 Cov.: 32 AF XY: 0.0000289 AC XY: 21 AN XY: 727162

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111902

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Pathogenic	0.85	D
Eigen	Uncertain	0.26
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.081	D
MetaRNN	Pathogenic	0.83	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.64	N
PhyloP100		7.4
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.56
Sift	Benign	0.46	T
Sift4G	Benign	0.26	T
Polyphen		0.0030	B
Vest4		0.86
MutPred		0.67		Loss of stability (P = 0.0098)
MVP		0.88
MPC		0.46
ClinPred		0.39	T
GERP RS		4.7
Varity_R		0.67
gMVP		0.89
Mutation Taster		=30/70	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00025
dbscSNV1_RF	Benign	0.052
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

Other links and lift over

dbSNP: rs752410256; hg19: chr14-23599008;