NM_198976.4:c.6C>G

Variant names:

• chr20-58981315-C-G
• NM_198976.4:c.6C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198976.4(NELFCD):​c.6C>G​(p.Asp2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NELFCD NM_198976.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

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]

ENSG00000285091 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030492544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198976.4. 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.6C>G	p.Asp2Glu	missense	Exon 1 of 15	NP_945327.3	Q8IXH7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELFCD	ENST00000652272.2	MANE Select	c.6C>G	p.Asp2Glu	missense	Exon 1 of 15	ENSP00000499018.1	Q8IXH7-4
	NELFCD	ENST00000602795.6	TSL:1	c.60C>G	p.Asp20Glu	missense	Exon 1 of 15	ENSP00000473290.1	H0UI80
	NELFCD	ENST00000460601.5	TSL:1	n.39C>G		non_coding_transcript_exon	Exon 1 of 16	ENSP00000436783.2	X6RLT1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 947094 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 448002

African (AFR) AF: 0.00 AC: 0 AN: 18630

American (AMR) AF: 0.00 AC: 0 AN: 9302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7644

East Asian (EAS) AF: 0.00 AC: 0 AN: 12802

South Asian (SAS) AF: 0.00 AC: 0 AN: 21766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3520

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 830674

Other (OTH) AF: 0.00 AC: 0 AN: 32918

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.39
DANN	Benign	0.63
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.2
PrimateAI	Pathogenic	0.93	D
Sift4G	Benign	0.67	T
Vest4		0.15
MVP		0.30
MPC		0.62
ClinPred		0.079	T
GERP RS		-7.5
PromoterAI		-0.0020	Neutral
gMVP		0.16
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

hg19: chr20-57556370;