rs730882247

Positions:

• chr17-50277743-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_153229.3(TMEM92):​c.95+3A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TMEM92 NM_153229.3 splice_region, intron
• Scores: Splicing: ADA: 0.005940
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.44

Genes affected

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

TMEM92 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-50277743-A-G is Pathogenic according to our data. Variant chr17-50277743-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 183355.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr17-50277743-A-G is described in Lovd as [Likely_pathogenic]. Variant chr17-50277743-A-G is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM92	NM_153229.3	c.95+3A>G		splice_region_variant, intron_variant		ENST00000507382.2	NP_694961.2
TMEM92	NM_001168215.2	c.95+3A>G		splice_region_variant, intron_variant			NP_001161687.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM92	ENST00000507382.2	c.95+3A>G		splice_region_variant, intron_variant		1	NM_153229.3	ENSP00000425144.1
TMEM92	ENST00000300433.7	c.95+3A>G		splice_region_variant, intron_variant		1		ENSP00000300433.3
TMEM92	ENST00000511882.1	n.191+3A>G		splice_region_variant, intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hydrocephalus;C0557874:Global developmental delay;C0740279:Cerebellar atrophy;CN228276:Bilateral squint Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 01, 2014

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0059
dbscSNV1_RF	Benign	0.20
SpliceAI score (max)		0.050		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: rs730882247; hg19: chr17-48355104;