rs976272

Variant names:

• chr14-60982610-T-A
• rs976272
• NM_153811.3:c.208T>A

Your query was ambiguous. Multiple possible variants found:

• chr14-60982610-T-A
• chr14-60982610-T-C
• chr14-60982610-T-G

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. L70S) has been classified as Uncertain significance.

• 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
• Publications: 28 publications found

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]

ENSG00000258892 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153811.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A6	NM_153811.3	MANE Select	c.208T>A	p.Leu70Met	missense	Exon 2 of 16	NP_722518.2	Q8IZM9-1
	SLC38A6	NM_001172702.2		c.208T>A	p.Leu70Met	missense	Exon 2 of 17	NP_001166173.1	Q8IZM9-2
	SLC38A6	NR_033344.2		n.550T>A		non_coding_transcript_exon	Exon 2 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A6	ENST00000267488.9	TSL:1 MANE Select	c.208T>A	p.Leu70Met	missense	Exon 2 of 16	ENSP00000267488.4	Q8IZM9-1
	SLC38A6	ENST00000354886.6	TSL:1	c.208T>A	p.Leu70Met	missense	Exon 2 of 17	ENSP00000346959.2	Q8IZM9-2
	SLC38A6	ENST00000451406.5	TSL:1	c.193T>A	p.Leu65Met	missense	Exon 2 of 17	ENSP00000395851.1	A0A0C4DG39

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

GnomAD2 exomes AF: 0.917 AC: 230221 AN: 251022 AF XY: 0.918

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 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

African (AFR) AF: 0.881 AC: 29488 AN: 33462

American (AMR) AF: 0.837 AC: 37355 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 24828 AN: 26128

East Asian (EAS) AF: 0.723 AC: 28668 AN: 39668

South Asian (SAS) AF: 0.794 AC: 68310 AN: 86070

European-Finnish (FIN) AF: 0.991 AC: 52925 AN: 53410

Middle Eastern (MID) AF: 0.949 AC: 5364 AN: 5650

European-Non Finnish (NFE) AF: 0.987 AC: 1097311 AN: 1111928

Other (OTH) AF: 0.950 AC: 57371 AN: 60366

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

African (AFR) AF: 0.883 AC: 36676 AN: 41526

American (AMR) AF: 0.885 AC: 13535 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 3291 AN: 3472

East Asian (EAS) AF: 0.767 AC: 3965 AN: 5172

South Asian (SAS) AF: 0.779 AC: 3760 AN: 4826

European-Finnish (FIN) AF: 0.989 AC: 10501 AN: 10614

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67139 AN: 68042

Other (OTH) AF: 0.931 AC: 1966 AN: 2112

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 v4.9

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
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	5.4e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.0	N
PhyloP100		6.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.15
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.012	B
Vest4		0.071
MPC		0.017
ClinPred		0.015	T
GERP RS		4.5
PromoterAI		-0.0076	Neutral
Varity_R		0.19
gMVP		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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