dbSNP rs3732103: SLC66A3:c.475+53C>T (chr2-11172098-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_152391.5(SLC66A3):c.475+53C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,584,898 control chromosomes in the GnomAD database, including 236,812 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 19976 hom., cov: 31)

Exomes 𝑓: 0.55 ( 216836 hom. )

Consequence

SLC66A3
NM_152391.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.32

Publications

12 publications found

Variant links:

Genes affected

SLC66A3 (HGNC:28503): (solute carrier family 66 member 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC66A3 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 (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152391.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC66A3	NM_152391.5	MANE Select	c.475+53C>T	intron	N/A	NP_689604.1	Q8N755-1
SLC66A3	NM_001282710.2		c.475+53C>T	intron	N/A	NP_001269639.1	Q8N755-2
SLC66A3	NM_001282711.2		c.355-2870C>T	intron	N/A	NP_001269640.1	B5MC27

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC66A3	ENST00000295083.8	TSL:1 MANE Select	c.475+53C>T	intron	N/A	ENSP00000295083.3	Q8N755-1
SLC66A3	ENST00000441908.6	TSL:2	c.475+53C>T	intron	N/A	ENSP00000406148.2	Q8N755-2
SLC66A3	ENST00000402361.5	TSL:2	c.355-2870C>T	intron	N/A	ENSP00000384129.1	B5MC27

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77229

AN:

151650

Hom.:

19960

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.546

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.587

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.524

GnomAD4 exome

AF:

0.548

AC:

785376

AN:

1433128

Hom.:

216836

AF XY:

0.549

AC XY:

391856

AN XY:

714088

show subpopulations

African (AFR)

AF:

0.418

AC:

13694

AN:

32784

American (AMR)

AF:

0.478

AC:

20696

AN:

43342

Ashkenazi Jewish (ASJ)

AF:

0.591

AC:

15023

AN:

25438

East Asian (EAS)

AF:

0.460

AC:

18026

AN:

39216

South Asian (SAS)

AF:

0.531

AC:

45077

AN:

84926

European-Finnish (FIN)

AF:

0.485

AC:

25286

AN:

52130

Middle Eastern (MID)

AF:

0.569

AC:

3039

AN:

5342

European-Non Finnish (NFE)

AF:

0.561

AC:

612453

AN:

1090766

Other (OTH)

AF:

0.542

AC:

32082

AN:

59184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

14078

28155

42233

56310

70388

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16986

33972

50958

67944

84930

<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:

0.509

AC:

77291

AN:

151770

Hom.:

19976

Cov.:

AF XY:

0.505

AC XY:

37430

AN XY:

74128

show subpopulations

African (AFR)

AF:

0.425

AC:

17583

AN:

41346

American (AMR)

AF:

0.511

AC:

7778

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.587

AC:

2033

AN:

3462

East Asian (EAS)

AF:

0.451

AC:

2326

AN:

5152

South Asian (SAS)

AF:

0.540

AC:

2601

AN:

4820

European-Finnish (FIN)

AF:

0.477

AC:

5020

AN:

10518

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.562

AC:

38186

AN:

67932

Other (OTH)

AF:

0.523

AC:

1100

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1918

3836

5754

7672

9590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.551

Hom.:

13674

Bravo

AF:

0.507

Asia WGS

AF:

0.467

AC:

1626

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.5

(source)

DANN

Benign

0.46

PhyloP100

1.3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over