Genetic Variant TMEM217B:p.Phe75Leu (chr6-37212747-A-G) – 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.223T>C(p.Phe75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 683,002 control chromosomes in the GnomAD database, including 220,501 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 0.78 ( 46705 hom., cov: 31)

Exomes 𝑓: 0.81 ( 173796 hom. )

Consequence

TMEM217B
NM_001395378.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.124

Publications

11 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:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM217B	NM_001395378.1 link	c.223T>C	p.Phe75Leu	missense_variant	Exon 2 of 2	ENST00000497775.2	NP_001382307.1
TMEM217	NM_001286401.2 link	c.*219T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000651039.2	NP_001273330.1	Q8N7C4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM217B	ENST00000497775.2 link	c.223T>C	p.Phe75Leu	missense_variant	Exon 2 of 2	2	NM_001395378.1	ENSP00000499172.1		A0A494BZU4
TMEM217	ENST00000651039.2 link	c.*219T>C		3_prime_UTR_variant	Exon 3 of 3		NM_001286401.2	ENSP00000499204.1		Q8N7C4-2

Frequencies

GnomAD3 genomes

AF:

0.783

AC:

118970

AN:

151978

Hom.:

46683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.728

Gnomad AMI

AF:

0.886

Gnomad AMR

AF:

0.808

Gnomad ASJ

AF:

0.684

Gnomad EAS

AF:

0.890

Gnomad SAS

AF:

0.827

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.788

Gnomad NFE

AF:

0.804

Gnomad OTH

AF:

0.777

GnomAD2 exomes

AF:

0.814

AC:

112856

AN:

138656

AF XY:

0.813

show subpopulations

Gnomad AFR exome

AF:

0.734

Gnomad AMR exome

AF:

0.873

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.886

Gnomad FIN exome

AF:

0.789

Gnomad NFE exome

AF:

0.803

Gnomad OTH exome

AF:

0.798

GnomAD4 exome

AF:

0.808

AC:

428751

AN:

530906

Hom.:

173796

Cov.:

AF XY:

0.808

AC XY:

232834

AN XY:

288064

show subpopulations

African (AFR)

AF:

0.731

AC:

11169

AN:

15282

American (AMR)

AF:

0.863

AC:

29227

AN:

33870

Ashkenazi Jewish (ASJ)

AF:

0.688

AC:

13293

AN:

19328

East Asian (EAS)

AF:

0.919

AC:

27939

AN:

30390

South Asian (SAS)

AF:

0.823

AC:

50827

AN:

61754

European-Finnish (FIN)

AF:

0.791

AC:

26383

AN:

33336

Middle Eastern (MID)

AF:

0.806

AC:

3177

AN:

3942

European-Non Finnish (NFE)

AF:

0.801

AC:

243500

AN:

303808

Other (OTH)

AF:

0.796

AC:

23236

AN:

29196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

5291

10583

15874

21166

26457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1014

2028

3042

4056

5070

<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:

0.783

AC:

119043

AN:

152096

Hom.:

46705

Cov.:

AF XY:

0.781

AC XY:

58076

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.727

AC:

30178

AN:

41490

American (AMR)

AF:

0.808

AC:

12340

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.684

AC:

2375

AN:

3470

East Asian (EAS)

AF:

0.889

AC:

4605

AN:

5178

South Asian (SAS)

AF:

0.827

AC:

3988

AN:

4822

European-Finnish (FIN)

AF:

0.779

AC:

8238

AN:

10570

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.804

AC:

54640

AN:

67984

Other (OTH)

AF:

0.779

AC:

1644

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1284

2568

3851

5135

6419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.789

Hom.:

89473

Bravo

AF:

0.782

Asia WGS

AF:

0.834

AC:

2897

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.0

(source)

DANN

Benign

0.58

PhyloP100

0.12

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