chr16-68293186-C-T

Variant names:

• chr16-68293186-C-T
• rs11644360
• NM_003983.6:c.1023-1519C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003983.6(SLC7A6):​c.1023-1519C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,032 control chromosomes in the GnomAD database, including 17,212 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (17212 hom., cov: 32)
• Consequence: SLC7A6 NM_003983.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 9 publications found

Genes affected

SLC7A6 (HGNC:11064): (solute carrier family 7 member 6) Enables basic amino acid transmembrane transporter activity. Involved in basic amino acid transmembrane transport and ornithine transport. Located in intracellular membrane-bounded organelle and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A6OS (HGNC:25807): (solute carrier family 7 member 6 opposite strand) Predicted to be involved in developmental process. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in cytoplasm and nucleus. Implicated in progressive myoclonus epilepsy. [provided by Alliance of Genome Resources, Apr 2022]

SLC7A6OS Gene-Disease associations (from GenCC):

• epilepsy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• epilepsy, progressive myoclonic, 12

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A6	NM_003983.6	c.1023-1519C>T		intron_variant	Intron 7 of 10	ENST00000219343.11	NP_003974.3
SLC7A6	NM_001076785.3	c.1023-1519C>T		intron_variant	Intron 8 of 11		NP_001070253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A6	ENST00000219343.11	c.1023-1519C>T		intron_variant	Intron 7 of 10	1	NM_003983.6	ENSP00000219343.6

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65207 AN: 151914 Hom.: 17202 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.429 AC: 65228 AN: 152032 Hom.: 17212 Cov.: 32 AF XY: 0.429 AC XY: 31892 AN XY: 74288

African (AFR) AF: 0.115 AC: 4759 AN: 41464

American (AMR) AF: 0.562 AC: 8597 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1616 AN: 3470

East Asian (EAS) AF: 0.806 AC: 4164 AN: 5166

South Asian (SAS) AF: 0.418 AC: 2016 AN: 4826

European-Finnish (FIN) AF: 0.480 AC: 5058 AN: 10546

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.553 AC: 37547 AN: 67956

Other (OTH) AF: 0.456 AC: 964 AN: 2114

Alfa AF: 0.479 Hom.: 2396

Bravo AF: 0.427

Asia WGS AF: 0.499 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.37
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs11644360; hg19: chr16-68327089;