17-34579120-C-T

Position:

• chr17-34579120-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NR_160787.1(TMEM132E-DT):​n.250G>A 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 0.00143 in 1,367,046 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00074 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: TMEM132E-DT NR_160787.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.195

Genes affected

TMEM132E-DT (HGNC:34412): (TMEM132E divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM132E-DT	NR_160787.1	n.250G>A		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM132E-DT	ENST00000623254.1	n.250G>A		non_coding_transcript_exon_variant	1/2	1
TMEM132E-DT	ENST00000661426.1	n.30G>A		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes AF: 0.000737 AC: 112 AN: 152066 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000810 AC: 199 AN: 245610 Hom.: 0 AF XY: 0.000836 AC XY: 112 AN XY: 133998

Gnomad AFR exome AF: 0.000403

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000654

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00147

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.00152 AC: 1848 AN: 1214866 Hom.: 1 Cov.: 34 AF XY: 0.00154 AC XY: 929 AN XY: 602108

Gnomad4 AFR exome AF: 0.000342

Gnomad4 AMR exome AF: 0.000215

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000661

Gnomad4 FIN exome AF: 0.000188

Gnomad4 NFE exome AF: 0.00178

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.000736 AC: 112 AN: 152180 Hom.: 0 Cov.: 33 AF XY: 0.000605 AC XY: 45 AN XY: 74384

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.000824

EpiCase AF: 0.00131

EpiControl AF: 0.00207

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.161G>A (p.R54Q) alteration is located in exon 1 (coding exon 1) of the C17orf102 gene. This alteration results from a G to A substitution at nucleotide position 161, causing the arginine (R) at amino acid position 54 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.2
DANN	Uncertain	0.98

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs202213790; hg19: chr17-32906139; COSMIC: COSV58696308;