chr16-68296494-A-G

Position:

• chr16-68296494-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003983.6(SLC7A6):​c.1250A>G​(p.Lys417Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,614,158 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (9 hom.)
• Consequence: SLC7A6 NM_003983.6 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 7.32

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009230226).
• BP6: Variant 16-68296494-A-G is Benign according to our data. Variant chr16-68296494-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 719412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A6	NM_003983.6	c.1250A>G	p.Lys417Arg	missense_variant	9/11	ENST00000219343.11
SLC7A6	NM_001076785.3	c.1250A>G	p.Lys417Arg	missense_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A6	ENST00000219343.11	c.1250A>G	p.Lys417Arg	missense_variant	9/11	1	NM_003983.6	P1

Frequencies

GnomAD3 genomes AF: 0.00159 AC: 242 AN: 152174 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00273

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00164 AC: 412 AN: 251432 Hom.: 1 AF XY: 0.00174 AC XY: 237 AN XY: 135896

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000983

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00118

Gnomad FIN exome AF: 0.000740

Gnomad NFE exome AF: 0.00267

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00167 AC: 2440 AN: 1461866 Hom.: 9 Cov.: 32 AF XY: 0.00179 AC XY: 1300 AN XY: 727238

Gnomad4 AFR exome AF: 0.000388

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.000344

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00123

Gnomad4 FIN exome AF: 0.000880

Gnomad4 NFE exome AF: 0.00186

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152292 Hom.: 1 Cov.: 31 AF XY: 0.00144 AC XY: 107 AN XY: 74458

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00274

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00253 Hom.: 1

Bravo AF: 0.00138

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00186 AC: 16

ExAC AF: 0.00171 AC: 208

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00284

EpiControl AF: 0.00314

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.18	.;T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.0092	T;T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	-0.37	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.75	N;N
REVEL	Benign	0.26
Sift	Benign	0.068	T;T
Sift4G	Uncertain	0.056	T;T
Polyphen		0.0	B;B
Vest4		0.14
MVP		0.79
MPC		0.37
ClinPred		0.033	T
GERP RS		5.2
Varity_R		0.16
gMVP		0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs79087422; hg19: chr16-68330397;