dbSNP rs17750404: TMEM63C:c.542+90C>T (chr14-77233590-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020431.4(TMEM63C):c.542+90C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,374,606 control chromosomes in the GnomAD database, including 46,924 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 0.22 ( 4382 hom., cov: 30)

Exomes 𝑓: 0.26 ( 42542 hom. )

Consequence

TMEM63C
NM_020431.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.340

Publications

9 publications found

Variant links:

Genes affected

TMEM63C (HGNC:23787): (transmembrane protein 63C) Enables calcium activated cation channel activity. Involved in cation transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. Biomarker of focal segmental glomerulosclerosis. [provided by Alliance of Genome Resources, Apr 2022]

TMEM63C Gene-Disease associations (from GenCC):

spastic paraplegia 87, autosomal recessive
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

TMEM63C 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=-0.87).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020431.4. 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
	TMEM63C	NM_020431.4	MANE Select	c.542+90C>T		intron	N/A	NP_065164.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM63C	ENST00000298351.5	TSL:1 MANE Select	c.542+90C>T		intron	N/A	ENSP00000298351.4

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33293

AN:

151506

Hom.:

4372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0854

Gnomad AMI

AF:

0.368

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.238

Gnomad EAS

AF:

0.166

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.258

AC:

315199

AN:

1222980

Hom.:

42542

AF XY:

0.255

AC XY:

155934

AN XY:

612602

show subpopulations

African (AFR)

AF:

0.0796

AC:

2293

AN:

28794

American (AMR)

AF:

0.312

AC:

11851

AN:

37952

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

5757

AN:

24186

East Asian (EAS)

AF:

0.159

AC:

5850

AN:

36864

South Asian (SAS)

AF:

0.149

AC:

11427

AN:

76852

European-Finnish (FIN)

AF:

0.300

AC:

15041

AN:

50180

Middle Eastern (MID)

AF:

0.216

AC:

1148

AN:

5314

European-Non Finnish (NFE)

AF:

0.273

AC:

248741

AN:

910448

Other (OTH)

AF:

0.250

AC:

13091

AN:

52390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

11143

22286

33428

44571

55714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7732

15464

23196

30928

38660

<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:

0.220

AC:

33326

AN:

151626

Hom.:

4382

Cov.:

AF XY:

0.222

AC XY:

16457

AN XY:

74036

show subpopulations

African (AFR)

AF:

0.0855

AC:

3535

AN:

41332

American (AMR)

AF:

0.301

AC:

4576

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

825

AN:

3462

East Asian (EAS)

AF:

0.166

AC:

852

AN:

5144

South Asian (SAS)

AF:

0.157

AC:

750

AN:

4776

European-Finnish (FIN)

AF:

0.304

AC:

3195

AN:

10498

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.275

AC:

18680

AN:

67888

Other (OTH)

AF:

0.246

AC:

517

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1249

2498

3747

4996

6245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

346

692

1038

1384

1730

<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:

0.253

Hom.:

17920

Bravo

AF:

0.216

Asia WGS

AF:

0.172

AC:

595

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.2

(source)

DANN

Benign

0.51

PhyloP100

-0.34

Mutation Taster

=100/0

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