Genetic Variant NM_020431.4:c.*1157G>A (chr14-77257883-G-A) – 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.*1157G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,298 control chromosomes in the GnomAD database, including 1,171 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 0.11 ( 1170 hom., cov: 33)

Exomes 𝑓: 0.087 ( 1 hom. )

Consequence

TMEM63C
NM_020431.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.900

Publications

7 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 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.*1157G>A		3_prime_UTR	Exon 24 of 24	NP_065164.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM63C	ENST00000298351.5	TSL:1 MANE Select	c.*1157G>A		3_prime_UTR	Exon 24 of 24	ENSP00000298351.4

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16585

AN:

152088

Hom.:

1172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.103

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.0888

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.146

Gnomad OTH

AF:

0.125

GnomAD4 exome

AF:

0.0870

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0694

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.109

AC:

16570

AN:

152206

Hom.:

1170

Cov.:

AF XY:

0.109

AC XY:

8092

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0276

AC:

1145

AN:

41546

American (AMR)

AF:

0.123

AC:

1878

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

359

AN:

3472

East Asian (EAS)

AF:

0.190

AC:

980

AN:

5170

South Asian (SAS)

AF:

0.0889

AC:

429

AN:

4828

European-Finnish (FIN)

AF:

0.131

AC:

1386

AN:

10592

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.146

AC:

9946

AN:

67986

Other (OTH)

AF:

0.123

AC:

260

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

733

1466

2199

2932

3665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.131

Hom.:

2325

Bravo

AF:

0.107

Asia WGS

AF:

0.128

AC:

443

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.2

(source)

DANN

Benign

0.43

PhyloP100

0.90

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over