Genetic Variant NM_001195541.3:c.494-140T>C (chr7-99610253-T-C) – 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.494-140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 594,046 control chromosomes in the GnomAD database, including 3,768 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 0.087 ( 772 hom., cov: 32)

Exomes 𝑓: 0.11 ( 2996 hom. )

Consequence

TMEM225B
NM_001195541.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.206

Publications

25 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:

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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM225B	NM_001195541.3 link	c.494-140T>C		intron_variant	Intron 5 of 5	ENST00000431679.6	NP_001182470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM225B	ENST00000431679.6 link	c.494-140T>C		intron_variant	Intron 5 of 5	5	NM_001195541.3	ENSP00000492416.1		P0DP42
TMEM225B	ENST00000453227.5 link	c.494-140T>C		intron_variant	Intron 5 of 5	5		ENSP00000491691.1		P0DP42

Frequencies

GnomAD3 genomes

AF:

0.0872

AC:

13270

AN:

152166

Hom.:

771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.0679

Gnomad ASJ

AF:

0.112

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0404

Gnomad FIN

AF:

0.144

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.0837

GnomAD4 exome

AF:

0.106

AC:

46853

AN:

441762

Hom.:

2996

AF XY:

0.104

AC XY:

23903

AN XY:

230024

show subpopulations

African (AFR)

AF:

0.0244

AC:

308

AN:

12632

American (AMR)

AF:

0.0666

AC:

1243

AN:

18652

Ashkenazi Jewish (ASJ)

AF:

0.119

AC:

1549

AN:

12982

East Asian (EAS)

AF:

0.000161

AC:

AN:

31000

South Asian (SAS)

AF:

0.0422

AC:

1549

AN:

36746

European-Finnish (FIN)

AF:

0.151

AC:

4218

AN:

27896

Middle Eastern (MID)

AF:

0.103

AC:

197

AN:

1908

European-Non Finnish (NFE)

AF:

0.128

AC:

35260

AN:

274542

Other (OTH)

AF:

0.0994

AC:

2524

AN:

25404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1959

3918

5878

7837

9796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.0871

AC:

13268

AN:

152284

Hom.:

772

Cov.:

AF XY:

0.0865

AC XY:

6444

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0218

AC:

907

AN:

41570

American (AMR)

AF:

0.0678

AC:

1038

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.112

AC:

387

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5180

South Asian (SAS)

AF:

0.0406

AC:

196

AN:

4828

European-Finnish (FIN)

AF:

0.144

AC:

1527

AN:

10592

Middle Eastern (MID)

AF:

0.112

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8903

AN:

68022

Other (OTH)

AF:

0.0823

AC:

174

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

603

1206

1809

2412

3015

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

150

300

450

600

750

<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:

0.109

Hom.:

2915

Bravo

AF:

0.0797

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.5

(source)

DANN

Benign

0.40

PhyloP100

0.21

Splicing

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