rs886039795

Positions:

• chr17-7403142-CCACTCAGAGCCTGGTAGTAAAA-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000302422.4(TMEM256):​c.244_265del​(p.Phe82GlufsTer31) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMEM256 ENST00000302422.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.02

Genes affected

TMEM256 (HGNC:28618): (transmembrane protein 256) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

TMEM256-PLSCR3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-7403142-CCACTCAGAGCCTGGTAGTAAAA-C is Pathogenic according to our data. Variant chr17-7403142-CCACTCAGAGCCTGGTAGTAAAA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 266078.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM256	NM_152766.5	c.244_265del	p.Phe82GlufsTer31	frameshift_variant	4/4	ENST00000302422.4	NP_689979.1
TMEM256-PLSCR3	NR_037719.1	n.164+494_164+515del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM256	ENST00000302422.4	c.244_265del	p.Phe82GlufsTer31	frameshift_variant	4/4	1	NM_152766.5	ENSP00000301939	P1
TMEM256	ENST00000576017.1	c.*249_*270del		3_prime_UTR_variant	3/3	3		ENSP00000468314
TMEM256	ENST00000575427.1	n.217_238del		non_coding_transcript_exon_variant	2/2	2

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: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Asphyxiating thoracic dystrophy 3 Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

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

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LOF, autozygosity mapping -

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: rs886039795; hg19: chr17-7306461;