Genetic Variant ENST00000602795.6:c.52A>G (chr20-58981307-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000602795.6(NELFCD):c.52A>G(p.Ile18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000427 in 935,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

NELFCD
ENST00000602795.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0350

Publications

0 publications found

Variant links:

Genes affected

NELFCD (HGNC:15934): (negative elongation factor complex member C/D) The NELF complex of proteins interacts with the DSIF protein complex to repress transcriptional elongation by RNA polymerase II. The protein encoded by this gene is an essential part of the NELF complex. Alternative translation initiation site usage results in the formation of two isoforms with different N-termini. [provided by RefSeq, Jul 2008]

NELFCD links:

ENSG00000285091 (HGNC:):

ENSG00000285091 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.087222725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000602795.6. 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
	NELFCD	NM_198976.4	MANE Select	c.-3A>G		5_prime_UTR	Exon 1 of 15	NP_945327.3	Q8IXH7-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NELFCD	ENST00000602795.6	TSL:1	c.52A>G	p.Ile18Val	missense	Exon 1 of 15	ENSP00000473290.1	H0UI80
NELFCD	ENST00000652272.2	MANE Select	c.-3A>G		5_prime_UTR	Exon 1 of 15	ENSP00000499018.1	Q8IXH7-4
NELFCD	ENST00000460601.5	TSL:1	n.31A>G		non_coding_transcript_exon	Exon 1 of 16	ENSP00000436783.2	X6RLT1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000427

AC:

AN:

935944

Hom.:

Cov.:

AF XY:

0.00000453

AC XY:

AN XY:

441764

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

18366

American (AMR)

AF:

0.00

AC:

AN:

8250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7380

East Asian (EAS)

AF:

0.00

AC:

AN:

11710

South Asian (SAS)

AF:

0.0000473

AC:

AN:

21160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8908

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3254

European-Non Finnish (NFE)

AF:

0.00000364

AC:

AN:

824464

Other (OTH)

AF:

0.00

AC:

AN:

32452

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00955443), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.388

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.79

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.0

PhyloP100

-0.035

PrimateAI

Pathogenic

0.92

Sift4G

Benign

0.30

Vest4

0.10

MVP

0.37

MPC

0.54

ClinPred

0.056

GERP RS

0.89

PromoterAI

-0.45

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.16

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over