dbSNP rs1224329: TMEM217B:p.Ser170Leu (chr6-37212461-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_001395378.1(TMEM217B):c.509C>T(p.Ser170Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 447,330 control chromosomes in the GnomAD database, including 137,595 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/6 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 0.74 ( 42402 hom., cov: 31)

Exomes 𝑓: 0.80 ( 95193 hom. )

Consequence

TMEM217B
NM_001395378.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.419

Publications

10 publications found

Variant links:

Genes affected

TMEM217B (HGNC:55922): (transmembrane protein 217B)

TMEM217B links:

TMEM217 (HGNC:21238): (transmembrane protein 217) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM217 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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM217B	NM_001395378.1 link	c.509C>T	p.Ser170Leu	missense_variant	Exon 2 of 2	ENST00000497775.2	NP_001382307.1
TMEM217	NM_001286401.2 link	c.*505C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000651039.2	NP_001273330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM217B	ENST00000497775.2 link	c.509C>T	p.Ser170Leu	missense_variant	Exon 2 of 2	2	NM_001395378.1	ENSP00000499172.1
TMEM217	ENST00000651039.2 link	c.*505C>T		3_prime_UTR_variant	Exon 3 of 3		NM_001286401.2	ENSP00000499204.1

Frequencies

GnomAD3 genomes

AF:

0.740

AC:

112429

AN:

151982

Hom.:

42383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.583

Gnomad AMI

AF:

0.886

Gnomad AMR

AF:

0.787

Gnomad ASJ

AF:

0.680

Gnomad EAS

AF:

0.889

Gnomad SAS

AF:

0.825

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.802

Gnomad OTH

AF:

0.735

GnomAD2 exomes

AF:

0.803

AC:

104513

AN:

130218

AF XY:

0.804

show subpopulations

Gnomad AFR exome

AF:

0.584

Gnomad AMR exome

AF:

0.861

Gnomad ASJ exome

AF:

0.674

Gnomad EAS exome

AF:

0.885

Gnomad FIN exome

AF:

0.789

Gnomad NFE exome

AF:

0.800

Gnomad OTH exome

AF:

0.787

GnomAD4 exome

AF:

0.801

AC:

236459

AN:

295230

Hom.:

95193

Cov.:

AF XY:

0.803

AC XY:

134895

AN XY:

167994

show subpopulations

African (AFR)

AF:

0.587

AC:

4975

AN:

8482

American (AMR)

AF:

0.861

AC:

22776

AN:

26456

Ashkenazi Jewish (ASJ)

AF:

0.676

AC:

6764

AN:

10004

East Asian (EAS)

AF:

0.893

AC:

8134

AN:

9112

South Asian (SAS)

AF:

0.821

AC:

47986

AN:

58442

European-Finnish (FIN)

AF:

0.794

AC:

9885

AN:

12452

Middle Eastern (MID)

AF:

0.802

AC:

2097

AN:

2616

European-Non Finnish (NFE)

AF:

0.800

AC:

122963

AN:

153768

Other (OTH)

AF:

0.783

AC:

10879

AN:

13898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

2432

4864

7295

9727

12159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.740

AC:

112486

AN:

152100

Hom.:

42402

Cov.:

AF XY:

0.739

AC XY:

54935

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.583

AC:

24145

AN:

41444

American (AMR)

AF:

0.788

AC:

12031

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.680

AC:

2361

AN:

3470

East Asian (EAS)

AF:

0.889

AC:

4600

AN:

5176

South Asian (SAS)

AF:

0.825

AC:

3977

AN:

4822

European-Finnish (FIN)

AF:

0.779

AC:

8245

AN:

10586

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.802

AC:

54539

AN:

68006

Other (OTH)

AF:

0.737

AC:

1559

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1402

2804

4207

5609

7011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<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:

0.778

Hom.:

135659

Bravo

AF:

0.732

Asia WGS

AF:

0.825

AC:

2866

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.55

PhyloP100

0.42

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