16-87836522-C-G

Variant names:

• chr16-87836522-C-G
• rs769384114
• NM_003486.7:c.1266G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003486.7(SLC7A5):​c.1266G>C​(p.Lys422Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC7A5 NM_003486.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.1266G>C	p.Lys422Asn	missense	Exon 8 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.1266G>C	p.Lys422Asn	missense	Exon 8 of 10	ENSP00000261622.4	Q01650
	SLC7A5	ENST00000565644.6	TSL:1	c.468G>C	p.Lys156Asn	missense	Exon 8 of 10	ENSP00000454323.1	A0A0C4DGL4
	SLC7A5	ENST00000850914.1		c.1320G>C	p.Lys440Asn	missense	Exon 8 of 10	ENSP00000520997.1	A0ABJ7H8K0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.076
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Benign	2.0	M
PhyloP100		1.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.013	D
Sift4G	Benign	0.072	T
Polyphen		0.77	P
Vest4		0.57
MutPred		0.45		Loss of methylation at K422 (P = 0.0096)
MVP		0.87
MPC		1.8
ClinPred		0.82	D
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.70
gMVP		0.81

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: rs769384114; hg19: chr16-87870128;