chr14-77257629-G-T

Variant names:

• chr14-77257629-G-T
• rs11847091
• NM_020431.4:c.*903G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020431.4(TMEM63C):​c.*903G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,156 control chromosomes in the GnomAD database, including 4,313 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 0.21 (4313 hom., cov: 32)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: TMEM63C NM_020431.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 7 publications found

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: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.28 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM63C	NM_020431.4	MANE Select	c.*903G>T		3_prime_UTR	Exon 24 of 24	NP_065164.2	Q9P1W3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM63C	ENST00000298351.5	TSL:1 MANE Select	c.*903G>T		3_prime_UTR	Exon 24 of 24	ENSP00000298351.4	Q9P1W3
	TMEM63C	ENST00000890516.1		c.*903G>T		3_prime_UTR	Exon 24 of 24	ENSP00000560575.1
	TMEM63C	ENST00000890513.1		c.*903G>T		3_prime_UTR	Exon 25 of 25	ENSP00000560572.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32223 AN: 151990 Hom.: 4310 Cov.: 32

Gnomad AFR AF: 0.0659

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.0438

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.146 AC: 7 AN: 48 Hom.: 0 Cov.: 0 AF XY: 0.0667 AC XY: 2 AN XY: 30

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 7 AN: 42

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.212 AC: 32228 AN: 152108 Hom.: 4313 Cov.: 32 AF XY: 0.213 AC XY: 15833 AN XY: 74376

African (AFR) AF: 0.0657 AC: 2725 AN: 41508

American (AMR) AF: 0.228 AC: 3478 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 806 AN: 3466

East Asian (EAS) AF: 0.0439 AC: 227 AN: 5172

South Asian (SAS) AF: 0.283 AC: 1365 AN: 4822

European-Finnish (FIN) AF: 0.345 AC: 3649 AN: 10576

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19229 AN: 67962

Other (OTH) AF: 0.208 AC: 439 AN: 2112

Alfa AF: 0.241 Hom.: 7345

Bravo AF: 0.195

Asia WGS AF: 0.154 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.80
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11847091; hg19: chr14-77723972;