chr14-60982610-T-A

Position:

• chr14-60982610-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153811.3(SLC38A6):​c.208T>A​(p.Leu70Met) variant causes a missense change. The variant allele was found at a frequency of 0.957 in 1,613,574 control chromosomes in the GnomAD database, including 742,354 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.93 (66617 hom., cov: 32)
  • Exomes 𝑓: 0.96 (675737 hom.)
• Consequence: SLC38A6 NM_153811.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.84

Genes affected

SLC38A6 (HGNC:19863): (solute carrier family 38 member 6) Predicted to enable L-glutamine transmembrane transporter activity. Predicted to be involved in amino acid transmembrane transport and glutamine transport. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC38A6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.409261E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC38A6	NM_153811.3	c.208T>A	p.Leu70Met	missense_variant	2/16	ENST00000267488.9	NP_722518.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC38A6	ENST00000267488.9	c.208T>A	p.Leu70Met	missense_variant	2/16	1	NM_153811.3	ENSP00000267488.4

Frequencies

GnomAD3 genomes AF: 0.933 AC: 141919 AN: 152148 Hom.: 66575 Cov.: 32

Gnomad AFR AF: 0.883

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.948

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.989

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.935

GnomAD3 exomes AF: 0.917 AC: 230221 AN: 251022 Hom.: 106581 AF XY: 0.918 AC XY: 124536 AN XY: 135652

Gnomad AFR exome AF: 0.882

Gnomad AMR exome AF: 0.832

Gnomad ASJ exome AF: 0.950

Gnomad EAS exome AF: 0.782

Gnomad SAS exome AF: 0.788

Gnomad FIN exome AF: 0.991

Gnomad NFE exome AF: 0.986

Gnomad OTH exome AF: 0.943

GnomAD4 exome AF: 0.959 AC: 1401620 AN: 1461308 Hom.: 675737 Cov.: 48 AF XY: 0.955 AC XY: 694304 AN XY: 726894

Gnomad4 AFR exome AF: 0.881

Gnomad4 AMR exome AF: 0.837

Gnomad4 ASJ exome AF: 0.950

Gnomad4 EAS exome AF: 0.723

Gnomad4 SAS exome AF: 0.794

Gnomad4 FIN exome AF: 0.991

Gnomad4 NFE exome AF: 0.987

Gnomad4 OTH exome AF: 0.950

GnomAD4 genome AF: 0.933 AC: 142021 AN: 152266 Hom.: 66617 Cov.: 32 AF XY: 0.928 AC XY: 69077 AN XY: 74458

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.885

Gnomad4 ASJ AF: 0.948

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.779

Gnomad4 FIN AF: 0.989

Gnomad4 NFE AF: 0.987

Gnomad4 OTH AF: 0.931

Alfa AF: 0.974 Hom.: 18506

Bravo AF: 0.925

TwinsUK AF: 0.988 AC: 3662

ALSPAC AF: 0.986 AC: 3799

ESP6500AA AF: 0.873 AC: 3846

ESP6500EA AF: 0.984 AC: 8460

ExAC AF: 0.918 AC: 111508

Asia WGS AF: 0.769 AC: 2675 AN: 3478

EpiCase AF: 0.984

EpiControl AF: 0.985

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.84
DEOGEN2	Benign	0.062	.;T;T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.57	T;T;T;T
MetaRNN	Benign	5.4e-7	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	N;N;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	2.7	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.012	B;B;.;.
Vest4		0.071
MPC		0.017
ClinPred		0.015	T
GERP RS		4.5
Varity_R		0.19
gMVP		0.49

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: rs976272; hg19: chr14-61449328; COSMIC: COSV50781573; COSMIC: COSV50781573;