17-50281058-A-G

Position:

• chr17-50281058-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153229.3(TMEM92):​c.*1750A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,022 control chromosomes in the GnomAD database, including 43,328 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 0.75 (43320 hom., cov: 31)
  • Exomes 𝑓: 0.64 (8 hom.)
• Consequence: TMEM92 NM_153229.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170

Genes affected

TMEM92 (HGNC:26579): (transmembrane protein 92) Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM92	NM_153229.3	c.*1750A>G		3_prime_UTR_variant	5/5	ENST00000507382.2	NP_694961.2
TMEM92	NM_001168215.2	c.*1750A>G		3_prime_UTR_variant	6/6		NP_001161687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM92	ENST00000507382.2	c.*1750A>G		3_prime_UTR_variant	5/5	1	NM_153229.3	ENSP00000425144.1
TMEM92	ENST00000300433.7	c.*1750A>G		3_prime_UTR_variant	6/6	1		ENSP00000300433.3

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114088 AN: 151868 Hom.: 43268 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.702

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.735

GnomAD4 exome AF: 0.639 AC: 23 AN: 36 Hom.: 8 Cov.: 0 AF XY: 0.667 AC XY: 16 AN XY: 24

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.751 AC: 114201 AN: 151986 Hom.: 43320 Cov.: 31 AF XY: 0.747 AC XY: 55499 AN XY: 74300

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.702

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.737

Alfa AF: 0.711 Hom.: 49889

Bravo AF: 0.756

Asia WGS AF: 0.754 AC: 2622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.34

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

LitVar

Other links and lift over

dbSNP: rs2254177; hg19: chr17-48358419;