14-49789165-T-TCTACA

Position:

• chr14-49789165-T-TCTACA

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_004713.6(NEMF):​c.2875_2876insTGTAG​(p.Asp959ValfsTer2) variant causes a stop gained, frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NEMF NM_004713.6 stop_gained, frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 3.81

Genes affected

NEMF (HGNC:10663): (nuclear export mediator factor) This gene encodes a component of the ribosome quality control complex. The encoded protein facilitates the recognition and ubiquitination of stalled 60S subunits by the ubiquitin ligase listerin. A similar protein in fly functions as a tumor suppressor. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-49789165-T-TCTACA is Pathogenic according to our data. Variant chr14-49789165-T-TCTACA is described in ClinVar as [Pathogenic]. Clinvar id is 986402.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEMF	NM_004713.6	c.2875_2876insTGTAG	p.Asp959ValfsTer2	stop_gained, frameshift_variant	28/33	ENST00000298310.10	NP_004704.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEMF	ENST00000298310.10	c.2875_2876insTGTAG	p.Asp959ValfsTer2	stop_gained, frameshift_variant	28/33	5	NM_004713.6	ENSP00000298310	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

See cases Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Medical Genetics, Taibah University College of Applied Medical Sciences

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Intellectual developmental disorder with speech delay and axonal peripheral neuropathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 08, 2021

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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: rs1890324880; hg19: chr14-50255883;