16-87837853-C-T

Variant names:

• chr16-87837853-C-T
• rs183791552
• NM_003486.7:c.1132G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003486.7(SLC7A5):​c.1132G>A​(p.Val378Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,604,358 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000023 (1 hom.)
• Consequence: SLC7A5 NM_003486.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.159
• Publications: 1 publications found

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]

SLC7A5 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics

SLC7A5-AS1 (HGNC:58301):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.049068987).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003486.7. 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
	SLC7A5	NM_003486.7	MANE Select	c.1132G>A	p.Val378Met	missense	Exon 7 of 10	NP_003477.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A5	ENST00000261622.5	TSL:1 MANE Select	c.1132G>A	p.Val378Met	missense	Exon 7 of 10	ENSP00000261622.4	Q01650
	SLC7A5	ENST00000565644.6	TSL:1	c.334G>A	p.Val112Met	missense	Exon 7 of 10	ENSP00000454323.1	A0A0C4DGL4
	SLC7A5	ENST00000850914.1		c.1186G>A	p.Val396Met	missense	Exon 7 of 10	ENSP00000520997.1	A0ABJ7H8K0

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152204 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000691 AC: 16 AN: 231640 AF XY: 0.0000642

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000616

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000753

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000948

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000227 AC: 33 AN: 1452036 Hom.: 1 Cov.: 31 AF XY: 0.0000222 AC XY: 16 AN XY: 720978

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.0000232 AC: 1 AN: 43068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25752

East Asian (EAS) AF: 0.000356 AC: 14 AN: 39370

South Asian (SAS) AF: 0.00 AC: 0 AN: 83544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52246

Middle Eastern (MID) AF: 0.00244 AC: 14 AN: 5734

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1108774

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152322 Hom.: 0 Cov.: 34 AF XY: 0.0000805 AC XY: 6 AN XY: 74490

African (AFR) AF: 0.00 AC: 0 AN: 41570

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000248 AC: 3

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	0.16
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.049	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.63	N
PhyloP100		-0.16
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.23
Sift	Benign	0.039	D
Sift4G	Benign	0.14	T
Polyphen		0.77	P
Vest4		0.57
MVP		0.48
MPC		0.88
ClinPred		0.060	T
GERP RS		0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.33
gMVP		0.41
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs183791552; hg19: chr16-87871459; COSMIC: COSV55365266; COSMIC: COSV55365266;