Genetic Variant NM_018976.5:c.542C>T (chr12-46366885-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_018976.5(SLC38A2):c.542C>T(p.Thr181Met) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,613,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

SLC38A2
NM_018976.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.77

Publications

1 publications found

Variant links:

Genes affected

SLC38A2 (HGNC:13448): (solute carrier family 38 member 2) Enables neutral amino acid:sodium symporter activity. Involved in several processes, including amino acid transport; cellular response to arsenite(3-); and positive regulation of RNA splicing. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC38A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054722697).

BP6

Variant 12-46366885-G-A is Benign according to our data. Variant chr12-46366885-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3797694.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018976.5. 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
	SLC38A2	NM_018976.5	MANE Select	c.542C>T	p.Thr181Met	missense	Exon 7 of 16	NP_061849.2
	SLC38A2	NM_001307936.2		c.242C>T	p.Thr81Met	missense	Exon 6 of 15	NP_001294865.1	Q96QD8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC38A2	ENST00000256689.10	TSL:1 MANE Select	c.542C>T	p.Thr181Met	missense	Exon 7 of 16	ENSP00000256689.5	Q96QD8-1
SLC38A2	ENST00000612232.1	TSL:1	c.242C>T	p.Thr81Met	missense	Exon 4 of 13	ENSP00000482873.1	Q96QD8-2
SLC38A2	ENST00000901221.1		c.542C>T	p.Thr181Met	missense	Exon 6 of 15	ENSP00000571280.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

250732

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461250

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

726900

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33446

American (AMR)

AF:

0.0000448

AC:

AN:

44604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000349

AC:

AN:

86054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000423

AC:

AN:

1111804

Other (OTH)

AF:

0.0000166

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41538

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.018

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.30

M_CAP

Benign

0.051

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.78

MutationAssessor

Benign

-1.6

PhyloP100

4.8

PrimateAI

Benign

0.48

PROVEAN

Benign

3.1

REVEL

Benign

0.11

Sift

Benign

0.80

Sift4G

Benign

0.63

Polyphen

0.0

Vest4

0.34

MVP

0.043

MPC

0.20

ClinPred

0.079

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.082

gMVP

0.37

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over