dbSNP rs204468: CLPTM1:p.Gly331Gly (chr19-44987378-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001294.4(CLPTM1):c.993T>C(p.Gly331Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,613,712 control chromosomes in the GnomAD database, including 303,703 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 0.53 ( 22506 hom., cov: 34)

Exomes 𝑓: 0.62 ( 281197 hom. )

Consequence

CLPTM1
NM_001294.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -8.05

Publications

33 publications found

Variant links:

Genes affected

CLPTM1 (HGNC:2087): (CLPTM1 regulator of GABA type A receptor forward trafficking) Predicted to be involved in regulation of T cell differentiation in thymus. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLPTM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP7

Synonymous conserved (PhyloP=-8.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLPTM1	NM_001294.4 link	c.993T>C	p.Gly331Gly	synonymous_variant	Exon 8 of 14	ENST00000337392.10	NP_001285.1	O96005-1A0A0S2Z3H2
CLPTM1	NM_001282175.2 link	c.951T>C	p.Gly317Gly	synonymous_variant	Exon 8 of 14		NP_001269104.1	O96005-4
CLPTM1	NM_001282176.2 link	c.687T>C	p.Gly229Gly	synonymous_variant	Exon 8 of 14		NP_001269105.1	O96005-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLPTM1	ENST00000337392.10 link	c.993T>C	p.Gly331Gly	synonymous_variant	Exon 8 of 14	1	NM_001294.4	ENSP00000336994.4		O96005-1

Frequencies

GnomAD3 genomes

AF:

0.527

AC:

80084

AN:

152038

Hom.:

22494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.633

Gnomad AMR

AF:

0.488

Gnomad ASJ

AF:

0.612

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.610

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.635

Gnomad OTH

AF:

0.536

GnomAD2 exomes

AF:

0.568

AC:

142622

AN:

251188

AF XY:

0.582

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.433

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.449

Gnomad FIN exome

AF:

0.583

Gnomad NFE exome

AF:

0.635

Gnomad OTH exome

AF:

0.587

GnomAD4 exome

AF:

0.616

AC:

900323

AN:

1461556

Hom.:

281197

Cov.:

AF XY:

0.618

AC XY:

449370

AN XY:

727070

show subpopulations

African (AFR)

AF:

0.336

AC:

11252

AN:

33474

American (AMR)

AF:

0.439

AC:

19609

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.605

AC:

15802

AN:

26134

East Asian (EAS)

AF:

0.428

AC:

16970

AN:

39690

South Asian (SAS)

AF:

0.637

AC:

54966

AN:

86246

European-Finnish (FIN)

AF:

0.587

AC:

31305

AN:

53294

Middle Eastern (MID)

AF:

0.601

AC:

3468

AN:

5766

European-Non Finnish (NFE)

AF:

0.640

AC:

711240

AN:

1111862

Other (OTH)

AF:

0.591

AC:

35711

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

18148

36296

54444

72592

90740

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18652

37304

55956

74608

93260

<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:

0.527

AC:

80120

AN:

152156

Hom.:

22506

Cov.:

AF XY:

0.526

AC XY:

39103

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.341

AC:

14140

AN:

41520

American (AMR)

AF:

0.488

AC:

7465

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.612

AC:

2125

AN:

3470

East Asian (EAS)

AF:

0.432

AC:

2232

AN:

5166

South Asian (SAS)

AF:

0.611

AC:

2950

AN:

4826

European-Finnish (FIN)

AF:

0.581

AC:

6145

AN:

10572

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.635

AC:

43172

AN:

67990

Other (OTH)

AF:

0.535

AC:

1130

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1877

3754

5631

7508

9385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

712

1424

2136

2848

3560

<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:

0.586

Hom.:

66240

Bravo

AF:

0.508

Asia WGS

AF:

0.495

AC:

1722

AN:

3478

EpiCase

AF:

0.630

EpiControl

AF:

0.626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.11

(source)

DANN

Benign

0.41

PhyloP100

-8.0

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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