dbSNP rs10504982: TMEM69P1:n.160A>G (chr8-97853094-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 ENST00000603405.1(TMEM69P1):n.160A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,328,262 control chromosomes in the GnomAD database, including 1,326 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 0.062 ( 678 hom., cov: 33)

Exomes 𝑓: 0.018 ( 648 hom. )

Consequence

TMEM69P1
ENST00000603405.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.321

Publications

0 publications found

Variant links:

COSMIC-nc: COSV71453890

Genes affected

TMEM69P1 (HGNC:56807): (TMEM69 pseudogene 1)

TMEM69P1 links:

LAPTM4B (HGNC:13646): (lysosomal protein transmembrane 4 beta) Enables ceramide binding activity; enzyme binding activity; and phosphatidylinositol bisphosphate binding activity. Involved in several processes, including negative regulation of macromolecule metabolic process; regulation of lysosomal membrane permeability; and regulation of lysosome organization. Located in several cellular components, including endosome; lysosomal membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LAPTM4B 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=-0.7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM69P1		n.97853094T>C		intragenic_variant
LAPTM4B	NM_018407.6 link	c.*1620T>C		downstream_gene_variant		ENST00000521545.7	NP_060877.4	Q86VI4-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM69P1	ENST00000603405.1 link	n.160A>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
LAPTM4B	ENST00000521545.7 link	c.*1620T>C	downstream_gene_variant		1	NM_018407.6	ENSP00000428409.1	Q86VI4-2
LAPTM4B	ENST00000445593.6 link	c.*1620T>C	downstream_gene_variant		1		ENSP00000402301.2	Q86VI4-3

Frequencies

GnomAD3 genomes

AF:

0.0624

AC:

9490

AN:

152154

Hom.:

678

Cov.:

show subpopulations

Gnomad AFR

AF:

0.175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0229

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0279

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.0483

GnomAD4 exome

AF:

0.0175

AC:

20626

AN:

1175990

Hom.:

648

Cov.:

AF XY:

0.0173

AC XY:

10350

AN XY:

597312

show subpopulations

African (AFR)

AF:

0.164

AC:

4402

AN:

26912

American (AMR)

AF:

0.0165

AC:

710

AN:

43048

Ashkenazi Jewish (ASJ)

AF:

0.0195

AC:

469

AN:

24066

East Asian (EAS)

AF:

0.0963

AC:

3643

AN:

37822

South Asian (SAS)

AF:

0.0197

AC:

1553

AN:

78644

European-Finnish (FIN)

AF:

0.0244

AC:

1241

AN:

50894

Middle Eastern (MID)

AF:

0.0210

AC:

108

AN:

5142

European-Non Finnish (NFE)

AF:

0.00840

AC:

7219

AN:

859114

Other (OTH)

AF:

0.0254

AC:

1281

AN:

50348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

791

1582

2374

3165

3956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.0624

AC:

9507

AN:

152272

Hom.:

678

Cov.:

AF XY:

0.0625

AC XY:

4656

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.175

AC:

7272

AN:

41534

American (AMR)

AF:

0.0228

AC:

349

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

AN:

3468

East Asian (EAS)

AF:

0.111

AC:

575

AN:

5192

South Asian (SAS)

AF:

0.0275

AC:

133

AN:

4830

European-Finnish (FIN)

AF:

0.0261

AC:

277

AN:

10620

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0106

AC:

719

AN:

68024

Other (OTH)

AF:

0.0473

AC:

100

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

429

857

1286

1714

2143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0144

Hom.:

Bravo

AF:

0.0687

Asia WGS

AF:

0.0830

AC:

289

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.8

(source)

DANN

Benign

0.80

PhyloP100

-0.32

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