Genetic Variant TMEM121:p.Pro299dup (chr14-105529712-T-TGCC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_025268.4(TMEM121):c.896_898dupCGC(p.Pro299dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 0)

Exomes 𝑓: 0.0022 ( 6 hom. )

Consequence

TMEM121
NM_025268.4 disruptive_inframe_insertion

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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM121	NM_025268.4	MANE Select	c.896_898dupCGC	p.Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	NP_079544.1	Q9BTD3
	TMEM121	NM_001331238.2		c.896_898dupCGC	p.Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	NP_001318167.1	Q9BTD3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM121	ENST00000392519.7	TSL:1 MANE Select	c.896_898dupCGC	p.Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000376304.2	Q9BTD3
TMEM121	ENST00000903730.1		c.896_898dupCGC	p.Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000573789.1
TMEM121	ENST00000903731.1		c.896_898dupCGC	p.Pro299dup	disruptive_inframe_insertion	Exon 2 of 2	ENSP00000573790.1

Frequencies

GnomAD3 genomes

AF:

0.00162

AC:

246

AN:

151668

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00448

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00209

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00194

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00191

AC:

227

AN:

118980

AF XY:

0.00196

show subpopulations

Gnomad AFR exome

AF:

0.000405

Gnomad AMR exome

AF:

0.00108

Gnomad ASJ exome

AF:

0.00678

Gnomad EAS exome

AF:

0.00282

Gnomad FIN exome

AF:

0.00305

Gnomad NFE exome

AF:

0.00157

Gnomad OTH exome

AF:

0.00219

GnomAD4 exome

AF:

0.00224

AC:

3088

AN:

1375870

Hom.:

Cov.:

AF XY:

0.00231

AC XY:

1566

AN XY:

678932

show subpopulations

African (AFR)

AF:

0.000131

AC:

AN:

30460

American (AMR)

AF:

0.000720

AC:

AN:

34706

Ashkenazi Jewish (ASJ)

AF:

0.00770

AC:

190

AN:

24672

East Asian (EAS)

AF:

0.00227

AC:

AN:

35168

South Asian (SAS)

AF:

0.00171

AC:

134

AN:

78372

European-Finnish (FIN)

AF:

0.00400

AC:

137

AN:

34258

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5378

European-Non Finnish (NFE)

AF:

0.00223

AC:

2400

AN:

1075448

Other (OTH)

AF:

0.00181

AC:

104

AN:

57408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

156

312

468

624

780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.00161

AC:

245

AN:

151776

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

124

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41372

American (AMR)

AF:

0.00170

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3466

East Asian (EAS)

AF:

0.00449

AC:

AN:

5118

South Asian (SAS)

AF:

0.00145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00209

AC:

AN:

10540

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00195

AC:

132

AN:

67860

Other (OTH)

AF:

0.00427

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00212

Hom.:

666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.50

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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