rs6499165

Variant names:

• chr16-68292297-A-C
• rs6499165
• NM_003983.6:c.1022+636A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-68292297-A-C
• chr16-68292297-A-G
• chr16-68292297-A-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.1022+636A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.795 in 152,182 control chromosomes in the GnomAD database, including 48,892 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 0.80 (48884 hom., cov: 31)
  • Exomes 𝑓: 0.61 (8 hom.)
• Consequence: SLC7A6 NM_003983.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 35 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]

ENSG00000279649 (HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A6	NM_003983.6	c.1022+636A>C		intron_variant	Intron 7 of 10	ENST00000219343.11	NP_003974.3
SLC7A6	NM_001076785.3	c.1022+636A>C		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.1022+636A>C		intron_variant	Intron 7 of 10	1	NM_003983.6	ENSP00000219343.6

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120909 AN: 152020 Hom.: 48823 Cov.: 31

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.772

GnomAD4 exome AF: 0.614 AC: 27 AN: 44 Hom.: 8 Cov.: 0 AF XY: 0.688 AC XY: 22 AN XY: 32

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.550 AC: 11 AN: 20

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.714 AC: 10 AN: 14

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.796 AC: 121032 AN: 152138 Hom.: 48884 Cov.: 31 AF XY: 0.793 AC XY: 58943 AN XY: 74362

African (AFR) AF: 0.946 AC: 39304 AN: 41542

American (AMR) AF: 0.784 AC: 11992 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2390 AN: 3472

East Asian (EAS) AF: 0.880 AC: 4543 AN: 5162

South Asian (SAS) AF: 0.715 AC: 3444 AN: 4816

European-Finnish (FIN) AF: 0.699 AC: 7389 AN: 10572

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49498 AN: 67966

Other (OTH) AF: 0.769 AC: 1624 AN: 2112

Alfa AF: 0.748 Hom.: 119226

Bravo AF: 0.809

Asia WGS AF: 0.772 AC: 2684 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.51
PhyloP100		-0.075
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6499165; hg19: chr16-68326200;