16-68291300-T-A

Position:

• chr16-68291300-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003983.6(SLC7A6):​c.886T>A​(p.Ser296Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,614,184 control chromosomes in the GnomAD database, including 287 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (155 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (132 hom.)
• Consequence: SLC7A6 NM_003983.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.864

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]

(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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018595755).
• BP6: Variant 16-68291300-T-A is Benign according to our data. Variant chr16-68291300-T-A is described in ClinVar as [Benign]. Clinvar id is 777037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A6	NM_003983.6	c.886T>A	p.Ser296Thr	missense_variant	6/11	ENST00000219343.11
SLC7A6	NM_001076785.3	c.886T>A	p.Ser296Thr	missense_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A6	ENST00000219343.11	c.886T>A	p.Ser296Thr	missense_variant	6/11	1	NM_003983.6	P1
	ENST00000623181.1	n.1491A>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0226 AC: 3439 AN: 152182 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.00578 AC: 1453 AN: 251416 Hom.: 56 AF XY: 0.00415 AC XY: 564 AN XY: 135872

Gnomad AFR exome AF: 0.0796

Gnomad AMR exome AF: 0.00336

Gnomad ASJ exome AF: 0.000198

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00245

GnomAD4 exome AF: 0.00240 AC: 3507 AN: 1461884 Hom.: 132 Cov.: 31 AF XY: 0.00208 AC XY: 1513 AN XY: 727248

Gnomad4 AFR exome AF: 0.0834

Gnomad4 AMR exome AF: 0.00385

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000243

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000773

Gnomad4 OTH exome AF: 0.00659

GnomAD4 genome AF: 0.0227 AC: 3463 AN: 152300 Hom.: 155 Cov.: 32 AF XY: 0.0222 AC XY: 1654 AN XY: 74474

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.00362 Hom.: 13

Bravo AF: 0.0257

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0758 AC: 333

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00728 AC: 884

Asia WGS AF: 0.00606 AC: 21 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.87
DEOGEN2	Benign	0.21	T;T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.56	.;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.76	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.55	N;N
REVEL	Benign	0.16
Sift	Benign	0.50	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0010	B;B
Vest4		0.26
MVP		0.60
MPC		0.41
ClinPred		0.0032	T
GERP RS		0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.098
gMVP		0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs62636648; hg19: chr16-68325203;