16-68274804-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003983.6(SLC7A6):c.78A>T(p.Glu26Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,614,138 control chromosomes in the GnomAD database, including 100 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (28 hom., cov: 31)
  • Exomes 𝑓: 0.0028 (72 hom.)
• Consequence: SLC7A6 NM_003983.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.05

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0025736094).
• BP6: Variant 16-68274804-A-T is Benign according to our data. Variant chr16-68274804-A-T is described in ClinVar as [Benign]. Clinvar id is 3059041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00604 (920/152304) while in subpopulation AMR AF= 0.0388 (593/15284). AF 95% confidence interval is 0.0362. There are 28 homozygotes in gnomad4. There are 540 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A6	NM_003983.6	c.78A>T	p.Glu26Asp	missense_variant	3/11	ENST00000219343.11
SLC7A6	NM_001076785.3	c.78A>T	p.Glu26Asp	missense_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A6	ENST00000219343.11	c.78A>T	p.Glu26Asp	missense_variant	3/11	1	NM_003983.6	P1

Frequencies

GnomAD3 genomes AF: 0.00601 AC: 914 AN: 152186 Hom.: 27 Cov.: 31

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0385

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0252

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00623

GnomAD3 exomes AF: 0.0104 AC: 2607 AN: 251468 Hom.: 56 AF XY: 0.00833 AC XY: 1132 AN XY: 135916

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0506

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0277

Gnomad SAS exome AF: 0.000653

Gnomad FIN exome AF: 0.0110

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.00733

GnomAD4 exome AF: 0.00276 AC: 4041 AN: 1461834 Hom.: 72 Cov.: 32 AF XY: 0.00255 AC XY: 1851 AN XY: 727216

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0251

Gnomad4 SAS exome AF: 0.000522

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.000150

Gnomad4 OTH exome AF: 0.00252

GnomAD4 genome AF: 0.00604 AC: 920 AN: 152304 Hom.: 28 Cov.: 31 AF XY: 0.00725 AC XY: 540 AN XY: 74472

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0253

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.00617

Alfa AF: 0.00152 Hom.: 0

Bravo AF: 0.00707

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00781 AC: 948

Asia WGS AF: 0.00837 AC: 29 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SLC7A6-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.14
Cadd	Benign	17
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0050	T;T;T;T;.;T;T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.58	T;.;T;T;T;T;T;T
MetaRNN	Benign	0.0026	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.60	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.29	T;T;D;T;.;T;T;T
Polyphen		0.044	.;B;.;B;.;.;.;.
Vest4		0.19
MutPred		0.14		Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);Loss of stability (P = 0.0959);
MPC		0.42
ClinPred		0.0068	T
GERP RS		0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.068
gMVP		0.17

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: rs62636644; hg19: chr16-68308707;