dbSNP rs2271622: SLC66A3:c.227-19C>T (chr2-11160606-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.227-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 1,613,580 control chromosomes in the GnomAD database, including 183,717 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 0.40 ( 13352 hom., cov: 31)

Exomes 𝑓: 0.48 ( 170365 hom. )

Consequence

SLC66A3
NM_152391.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.36

Publications

16 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

new If you want to explore the variant's impact on the transcript NM_152391.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.496 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.227-19C>T	intron	N/A	NP_689604.1	Q8N755-1
SLC66A3	NM_001282710.2		c.227-19C>T	intron	N/A	NP_001269639.1	Q8N755-2
SLC66A3	NM_001282711.2		c.227-19C>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.227-19C>T	intron	N/A	ENSP00000295083.3	Q8N755-1
SLC66A3	ENST00000441908.6	TSL:2	c.227-19C>T	intron	N/A	ENSP00000406148.2	Q8N755-2
SLC66A3	ENST00000445402.5	TSL:4	c.296-19C>T	intron	N/A	ENSP00000410430.1	C9J4B6

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60270

AN:

151814

Hom.:

13347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.193

Gnomad AMI

AF:

0.495

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.412

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.417

GnomAD2 exomes

AF:

0.454

AC:

114063

AN:

251476

AF XY:

0.462

show subpopulations

Gnomad AFR exome

AF:

0.182

Gnomad AMR exome

AF:

0.426

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.480

Gnomad FIN exome

AF:

0.424

Gnomad NFE exome

AF:

0.491

Gnomad OTH exome

AF:

0.479

GnomAD4 exome

AF:

0.479

AC:

700033

AN:

1461650

Hom.:

170365

Cov.:

AF XY:

0.480

AC XY:

349276

AN XY:

727144

show subpopulations

African (AFR)

AF:

0.183

AC:

6133

AN:

33480

American (AMR)

AF:

0.427

AC:

19097

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

10983

AN:

26132

East Asian (EAS)

AF:

0.467

AC:

18535

AN:

39700

South Asian (SAS)

AF:

0.498

AC:

42935

AN:

86254

European-Finnish (FIN)

AF:

0.427

AC:

22820

AN:

53416

Middle Eastern (MID)

AF:

0.495

AC:

2855

AN:

5768

European-Non Finnish (NFE)

AF:

0.493

AC:

548544

AN:

1111798

Other (OTH)

AF:

0.466

AC:

28131

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

20536

41073

61609

82146

102682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15932

31864

47796

63728

79660

<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:

0.397

AC:

60284

AN:

151930

Hom.:

13352

Cov.:

AF XY:

0.396

AC XY:

29410

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.193

AC:

8007

AN:

41462

American (AMR)

AF:

0.445

AC:

6792

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

1429

AN:

3470

East Asian (EAS)

AF:

0.463

AC:

2382

AN:

5146

South Asian (SAS)

AF:

0.513

AC:

2465

AN:

4806

European-Finnish (FIN)

AF:

0.414

AC:

4376

AN:

10562

Middle Eastern (MID)

AF:

0.493

AC:

144

AN:

292

European-Non Finnish (NFE)

AF:

0.491

AC:

33365

AN:

67936

Other (OTH)

AF:

0.417

AC:

874

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1736

3472

5207

6943

8679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

576

1152

1728

2304

2880

<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:

0.463

Hom.:

64716

Bravo

AF:

0.385

Asia WGS

AF:

0.448

AC:

1561

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.13

(source)

DANN

Benign

0.46

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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