Genetic Variant NELFCD:c.-11C>T (chr20-58981299-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198976.4(NELFCD):c.-11C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000371 in 1,077,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

NELFCD
NM_198976.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.646

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14639476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELFCD	NM_198976.4 link	c.-11C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 15	ENST00000652272.2	NP_945327.3	Q8IXH7-4H0UI80
NELFCD	NM_198976.4 link	c.-11C>T		5_prime_UTR_variant	Exon 1 of 15	ENST00000652272.2	NP_945327.3	Q8IXH7-4H0UI80
NELFCD	XM_047440188.1 link	c.44C>T	p.Pro15Leu	missense_variant	Exon 1 of 14		XP_047296144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELFCD	ENST00000652272 link	c.-11C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 15		NM_198976.4	ENSP00000499018.1		Q8IXH7-4
NELFCD	ENST00000652272 link	c.-11C>T		5_prime_UTR_variant	Exon 1 of 15		NM_198976.4	ENSP00000499018.1		Q8IXH7-4

Frequencies

GnomAD3 genomes

AF:

0.0000271

AC:

AN:

147708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000976

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000387

AC:

AN:

929324

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

438238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000551

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000402

Gnomad4 OTH exome

AF:

0.0000622

GnomAD4 genome

AF:

0.0000271

AC:

AN:

147708

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

71902

show subpopulations

Gnomad4 AFR

AF:

0.0000976

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.17C>T (p.P6L) alteration is located in exon 1 (coding exon 1) of the NELFCD gene. This alteration results from a C to T substitution at nucleotide position 17, causing the proline (P) at amino acid position 6 to be replaced by a leucine (L). 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

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.76

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

PrimateAI

Pathogenic

0.89

Sift4G

Benign

0.19

Vest4

0.27

MVP

0.30

MPC

0.66

ClinPred

0.24

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over