Genetic Variant TMEM121:p.Pro299del (chr14-105529712-TGCC-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_025268.4(TMEM121):c.896_898delCGC(p.Pro299del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,524,964 control chromosomes in the GnomAD database, including 66,989 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 13184 hom., cov: 0)

Exomes 𝑓: 0.27 ( 53805 hom. )

Consequence

TMEM121
NM_025268.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.501

Publications

18 publications found

Variant links:

Genes affected

TMEM121 (HGNC:20511): (transmembrane protein 121) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM121 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.644 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025268.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM121	NM_025268.4	MANE Select	c.896_898delCGC	p.Pro299del	disruptive_inframe_deletion	Exon 2 of 2	NP_079544.1
	TMEM121	NM_001331238.2		c.896_898delCGC	p.Pro299del	disruptive_inframe_deletion	Exon 2 of 2	NP_001318167.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM121	ENST00000392519.7	TSL:1 MANE Select	c.896_898delCGC	p.Pro299del	disruptive_inframe_deletion	Exon 2 of 2	ENSP00000376304.2

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

57185

AN:

151606

Hom.:

13129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.650

Gnomad AMI

AF:

0.171

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.250

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.338

GnomAD2 exomes

AF:

0.299

AC:

35606

AN:

118980

AF XY:

0.299

show subpopulations

Gnomad AFR exome

AF:

0.691

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.339

Gnomad EAS exome

AF:

0.546

Gnomad FIN exome

AF:

0.296

Gnomad NFE exome

AF:

0.262

Gnomad OTH exome

AF:

0.285

GnomAD4 exome

AF:

0.271

AC:

371787

AN:

1373250

Hom.:

53805

AF XY:

0.270

AC XY:

182936

AN XY:

677610

show subpopulations

African (AFR)

AF:

0.672

AC:

20439

AN:

30426

American (AMR)

AF:

0.196

AC:

6734

AN:

34428

Ashkenazi Jewish (ASJ)

AF:

0.337

AC:

8290

AN:

24610

East Asian (EAS)

AF:

0.395

AC:

13869

AN:

35134

South Asian (SAS)

AF:

0.261

AC:

20437

AN:

78190

European-Finnish (FIN)

AF:

0.296

AC:

10134

AN:

34230

Middle Eastern (MID)

AF:

0.276

AC:

1485

AN:

5374

European-Non Finnish (NFE)

AF:

0.254

AC:

272832

AN:

1073536

Other (OTH)

AF:

0.306

AC:

17567

AN:

57322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

15392

30783

46175

61566

76958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9514

19028

28542

38056

47570

<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:

0.378

AC:

57287

AN:

151714

Hom.:

13184

Cov.:

AF XY:

0.374

AC XY:

27719

AN XY:

74158

show subpopulations

African (AFR)

AF:

0.651

AC:

26913

AN:

41352

American (AMR)

AF:

0.237

AC:

3627

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

1216

AN:

3464

East Asian (EAS)

AF:

0.493

AC:

2522

AN:

5114

South Asian (SAS)

AF:

0.250

AC:

1207

AN:

4826

European-Finnish (FIN)

AF:

0.305

AC:

3217

AN:

10538

Middle Eastern (MID)

AF:

0.308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.260

AC:

17613

AN:

67834

Other (OTH)

AF:

0.344

AC:

726

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1607

3214

4821

6428

8035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.213

Hom.:

666

Bravo

AF:

0.390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.50

Mutation Taster

=86/14

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over