14-49785312-TA-GG

Variant names:

• chr14-49785312-TA-GG
• NM_004713.6:c.2936_2937delTAinsCC
• NEMF p.Leu979Pro

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004713.6(NEMF):​c.2936_2937delTAinsCC​(p.Leu979Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEMF NM_004713.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.52
• Publications: 0 publications found

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]

KLHDC2 (HGNC:20231): (kelch domain containing 2) Enables ubiquitin ligase-substrate adaptor activity. Involved in ubiquitin-dependent protein catabolic process via the C-end degron rule pathway. Located in nuclear body and nuclear membrane. Is active in Cul2-RING ubiquitin ligase complex and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004713.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEMF	NM_004713.6	MANE Select	c.2936_2937delTAinsCC	p.Leu979Pro	missense	N/A	NP_004704.3
	KLHDC2	NM_014315.3	MANE Select	c.*2359_*2360delTAinsGG		3_prime_UTR	Exon 13 of 13	NP_055130.1	Q9Y2U9-1
	NEMF	NM_001301732.3		c.2873_2874delTAinsCC	p.Leu958Pro	missense	N/A	NP_001288661.2	O60524-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEMF	ENST00000298310.10	TSL:5 MANE Select	c.2936_2937delTAinsCC	p.Leu979Pro	missense	N/A	ENSP00000298310.5	O60524-1
	KLHDC2	ENST00000298307.10	TSL:1 MANE Select	c.*2359_*2360delTAinsGG		3_prime_UTR	Exon 13 of 13	ENSP00000298307.5	Q9Y2U9-1
	NEMF	ENST00000556074.5	TSL:1	n.1760_1761delTAinsCC		non_coding_transcript_exon	Exon 9 of 10

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr14-50252030;