Genetic Variant NM_001170798.1:c.812C>T (chr12-16244743-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001170798.1(SLC15A5):c.812C>T(p.Pro271Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 1,537,704 control chromosomes in the GnomAD database, including 710,541 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.94 ( 67612 hom., cov: 33)

Exomes 𝑓: 0.96 ( 642929 hom. )

Consequence

SLC15A5
NM_001170798.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.71

Publications

18 publications found

Variant links:

Genes affected

SLC15A5 (HGNC:33455): (solute carrier family 15 member 5) Predicted to enable symporter activity. Predicted to be involved in peptide transport; protein transport; and transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC15A5 links:

LOC101928362 (HGNC:):

LOC101928362 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.3576243E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC15A5	NM_001170798.1 link	c.812C>T	p.Pro271Leu	missense_variant	Exon 4 of 9	ENST00000344941.3	NP_001164269.1
LOC101928362	XR_001749028.1 link	n.334-88G>A		intron_variant	Intron 4 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC15A5	ENST00000344941.3 link	c.812C>T	p.Pro271Leu	missense_variant	Exon 4 of 9	5	NM_001170798.1	ENSP00000340402.3

Frequencies

GnomAD3 genomes

AF:

0.941

AC:

143275

AN:

152188

Hom.:

67559

Cov.:

show subpopulations

Gnomad AFR

AF:

0.884

Gnomad AMI

AF:

0.974

Gnomad AMR

AF:

0.949

Gnomad ASJ

AF:

0.980

Gnomad EAS

AF:

0.994

Gnomad SAS

AF:

0.979

Gnomad FIN

AF:

0.940

Gnomad MID

AF:

0.972

Gnomad NFE

AF:

0.965

Gnomad OTH

AF:

0.956

GnomAD2 exomes

AF:

0.959

AC:

137981

AN:

143936

AF XY:

0.963

show subpopulations

Gnomad AFR exome

AF:

0.869

Gnomad AMR exome

AF:

0.934

Gnomad ASJ exome

AF:

0.982

Gnomad EAS exome

AF:

0.994

Gnomad FIN exome

AF:

0.940

Gnomad NFE exome

AF:

0.966

Gnomad OTH exome

AF:

0.968

GnomAD4 exome

AF:

0.963

AC:

1334468

AN:

1385398

Hom.:

642929

Cov.:

AF XY:

0.964

AC XY:

659183

AN XY:

683594

show subpopulations

African (AFR)

AF:

0.876

AC:

27667

AN:

31596

American (AMR)

AF:

0.936

AC:

33402

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.981

AC:

24713

AN:

25182

East Asian (EAS)

AF:

0.996

AC:

35580

AN:

35732

South Asian (SAS)

AF:

0.979

AC:

77536

AN:

79236

European-Finnish (FIN)

AF:

0.943

AC:

33188

AN:

35212

Middle Eastern (MID)

AF:

0.978

AC:

5572

AN:

5698

European-Non Finnish (NFE)

AF:

0.965

AC:

1040917

AN:

1078976

Other (OTH)

AF:

0.963

AC:

55893

AN:

58064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

2995

5990

8985

11980

14975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21264

42528

63792

85056

106320

<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:

0.941

AC:

143383

AN:

152306

Hom.:

67612

Cov.:

AF XY:

0.941

AC XY:

70108

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.884

AC:

36736

AN:

41536

American (AMR)

AF:

0.949

AC:

14525

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.980

AC:

3401

AN:

3472

East Asian (EAS)

AF:

0.994

AC:

5155

AN:

5188

South Asian (SAS)

AF:

0.979

AC:

4722

AN:

4824

European-Finnish (FIN)

AF:

0.940

AC:

9987

AN:

10622

Middle Eastern (MID)

AF:

0.973

AC:

286

AN:

294

European-Non Finnish (NFE)

AF:

0.965

AC:

65661

AN:

68034

Other (OTH)

AF:

0.956

AC:

2022

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

426

852

1277

1703

2129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.960

Hom.:

179820

Bravo

AF:

0.938

TwinsUK

AF:

0.969

AC:

3594

ALSPAC

AF:

0.969

AC:

3733

ESP6500AA

AF:

0.880

AC:

1218

ESP6500EA

AF:

0.966

AC:

3074

ExAC

AF:

0.956

AC:

21681

Asia WGS

AF:

0.980

AC:

3408

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.6

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.0010

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0000014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

PhyloP100

2.7

PrimateAI

Benign

0.29

PROVEAN

Benign

1.8

REVEL

Benign

0.070

Sift

Benign

0.54

Sift4G

Benign

1.0

Vest4

0.049

ClinPred

0.0080

GERP RS

2.4

Varity_R

0.025

gMVP

0.19

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over