NM_153811.3:c.752A>G

Variant names:

• chr14-61045353-A-G
• rs45523838
• NM_153811.3:c.752A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_153811.3(SLC38A6):​c.752A>G​(p.Tyr251Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000845 in 1,613,276 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00082 (4 hom.)
• Consequence: SLC38A6 NM_153811.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.51
• Publications: 5 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]

ENSG00000307460 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04082191).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.752A>G	p.Tyr251Cys	missense	Exon 11 of 16	NP_722518.2	Q8IZM9-1
	SLC38A6	NM_001172702.2		c.752A>G	p.Tyr251Cys	missense	Exon 11 of 17	NP_001166173.1	Q8IZM9-2
	SLC38A6	NR_033344.2		n.1094A>G		non_coding_transcript_exon	Exon 11 of 17

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC38A6	ENST00000267488.9	TSL:1 MANE Select	c.752A>G	p.Tyr251Cys	missense	Exon 11 of 16	ENSP00000267488.4	Q8IZM9-1
	SLC38A6	ENST00000354886.6	TSL:1	c.752A>G	p.Tyr251Cys	missense	Exon 11 of 17	ENSP00000346959.2	Q8IZM9-2
	SLC38A6	ENST00000451406.5	TSL:1	c.737A>G	p.Tyr246Cys	missense	Exon 11 of 17	ENSP00000395851.1	A0A0C4DG39

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 171 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00196

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00121 AC: 303 AN: 251112 AF XY: 0.00123

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00352

Gnomad NFE exome AF: 0.00188

Gnomad OTH exome AF: 0.000818

GnomAD4 exome AF: 0.000816 AC: 1192 AN: 1461020 Hom.: 4 Cov.: 29 AF XY: 0.000886 AC XY: 644 AN XY: 726876

African (AFR) AF: 0.0000299 AC: 1 AN: 33462

American (AMR) AF: 0.000134 AC: 6 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00390 AC: 208 AN: 53350

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.000832 AC: 925 AN: 1111442

Other (OTH) AF: 0.000646 AC: 39 AN: 60342

GnomAD4 genome AF: 0.00112 AC: 171 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.00106 AC XY: 79 AN XY: 74438

African (AFR) AF: 0.0000963 AC: 4 AN: 41546

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00245 AC: 26 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00196 AC: 133 AN: 68018

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00133 Hom.: 2

Bravo AF: 0.000635

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.00136 AC: 165

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.000982

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.5
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.89
MVP		0.26
MPC		0.14
ClinPred		0.27	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.90
gMVP		0.76
Mutation Taster		=76/24	polymorphism

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: rs45523838; hg19: chr14-61512071;