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GeneBe

14-49785313-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004713.6(NEMF):c.2936T>C(p.Leu979Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

NEMF
NM_004713.6 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.52
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NEMFNM_004713.6 linkuse as main transcriptc.2936T>C p.Leu979Pro missense_variant 30/33 ENST00000298310.10
KLHDC2NM_014315.3 linkuse as main transcriptc.*2360A>G 3_prime_UTR_variant 13/13 ENST00000298307.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NEMFENST00000298310.10 linkuse as main transcriptc.2936T>C p.Leu979Pro missense_variant 30/335 NM_004713.6 P1O60524-1
KLHDC2ENST00000298307.10 linkuse as main transcriptc.*2360A>G 3_prime_UTR_variant 13/131 NM_014315.3 P1Q9Y2U9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 20, 2023The c.2936T>C (p.L979P) alteration is located in exon 30 (coding exon 30) of the NEMF gene. This alteration results from a T to C substitution at nucleotide position 2936, causing the leucine (L) at amino acid position 979 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Benign
0.23
T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.79
T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Uncertain
0.59
D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Benign
1.7
L;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.7
D;D
REVEL
Uncertain
0.31
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.022
D;.
Polyphen
1.0
D;.
Vest4
0.66
MutPred
0.39
Loss of stability (P = 0.0012);.;
MVP
0.30
MPC
1.0
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.79
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-50252031; API