Genetic Variant TMEM225B:c.-85+69T>A (chr7-99598450-T-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_001195541.3(TMEM225B):c.-85+69T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,570 control chromosomes in the GnomAD database, including 1,579 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 0.13 ( 1578 hom., cov: 32)

Exomes 𝑓: 0.097 ( 1 hom. )

Consequence

TMEM225B
NM_001195541.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.00

Publications

21 publications found

Variant links:

Genes affected

TMEM225B (HGNC:53075): (transmembrane protein 225B) Predicted to be involved in negative regulation of phosphatase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM225B links:

ENSG00000272647 (HGNC:):

ENSG00000272647 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195541.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM225B	NM_001195541.3	MANE Select	c.-85+69T>A	intron	N/A	NP_001182470.1
TMEM225B	NM_001195542.3		c.-82+69T>A	intron	N/A	NP_001182471.1
TMEM225B	NM_001195543.3		c.-85+78T>A	intron	N/A	NP_001182472.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TMEM225B	ENST00000431679.6	TSL:5 MANE Select	c.-85+69T>A	intron	N/A	ENSP00000492416.1
ENSG00000272647	ENST00000455905.1	TSL:3	n.137-1758T>A	intron	N/A	ENSP00000401282.1
TMEM225B	ENST00000453227.5	TSL:5	c.-85+78T>A	intron	N/A	ENSP00000491691.1

Frequencies

GnomAD3 genomes

AF:

0.126

AC:

19139

AN:

152082

Hom.:

1571

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0974

Gnomad ASJ

AF:

0.0755

Gnomad EAS

AF:

0.00405

Gnomad SAS

AF:

0.0679

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0832

Gnomad OTH

AF:

0.116

GnomAD4 exome

AF:

0.0968

AC:

AN:

372

Hom.:

AF XY:

0.0851

AC XY:

AN XY:

282

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.111

AC:

AN:

296

Other (OTH)

AF:

0.111

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.126

AC:

19177

AN:

152198

Hom.:

1578

Cov.:

AF XY:

0.128

AC XY:

9513

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.226

AC:

9391

AN:

41532

American (AMR)

AF:

0.0972

AC:

1487

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0755

AC:

262

AN:

3468

East Asian (EAS)

AF:

0.00406

AC:

AN:

5172

South Asian (SAS)

AF:

0.0684

AC:

330

AN:

4828

European-Finnish (FIN)

AF:

0.160

AC:

1701

AN:

10602

Middle Eastern (MID)

AF:

0.0685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0832

AC:

5654

AN:

67986

Other (OTH)

AF:

0.123

AC:

260

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

831

1661

2492

3322

4153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<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:

0.114

Hom.:

160

Bravo

AF:

0.126

Asia WGS

AF:

0.0770

AC:

267

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

(source)

DANN

Benign

0.74

PhyloP100

-3.0

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over