rs869312734

chr17-32933275-TGGAGAATGAAGACTGGATCGAAGATGCCTCGTAA-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PP3 PP5

The NM_015544.3(TMEM98):c.236_263+6del variant causes a splice donor, splice donor region, coding sequence, intron change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM98 NM_015544.3 splice_donor, splice_donor_region, coding_sequence, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.57

Genes affected

TMEM98 (HGNC:24529): (transmembrane protein 98) This gene encodes a transmembrane protein. A missense mutation in this gene result in Nanophthalmos 4 (NNO4). Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.19236417 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 17-32933275-TGGAGAATGAAGACTGGATCGAAGATGCCTCGTAA-T is Pathogenic according to our data. Variant chr17-32933275-TGGAGAATGAAGACTGGATCGAAGATGCCTCGTAA-T is described in ClinVar as [Pathogenic]. Clinvar id is 224332.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM98	NM_015544.3	c.236_263+6del		splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant	4/8	ENST00000579849.6
TMEM98	NM_001033504.2	c.236_263+6del		splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant	3/7
TMEM98	NM_001301746.2	c.236_263+6del		splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM98	ENST00000579849.6	c.236_263+6del		splice_donor_variant, splice_donor_region_variant, coding_sequence_variant, intron_variant	4/8	1	NM_015544.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Nanophthalmos 4 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 10, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs869312734; hg19: chr17-31260293;