ENST00000480876.3:c.-257G>C

Variant names:

• chr9-132670191-C-G
• ENST00000480876.3:c.-257G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000480876.3(DDX31):​c.-257G>C variant causes a 5 prime UTR 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DDX31 ENST00000480876.3 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.348
• Publications: 0 publications found

Genes affected

DDX31 (HGNC:16715): (DEAD-box helicase 31) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a member of this family. The function of this member has not been determined. Alternative splicing of this gene generates multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2016]

GTF3C4 (HGNC:4667): (general transcription factor IIIC subunit 4) Predicted to enable enzyme activator activity. Predicted to contribute to DNA binding activity. Predicted to be involved in 5S class rRNA transcription by RNA polymerase III and tRNA transcription by RNA polymerase III. Located in mitochondrion and nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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=0.07345551).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000480876.3. 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
	GTF3C4	NR_133925.1		n.157C>G		non_coding_transcript_exon	Exon 1 of 6
	DDX31	NM_022779.9	MANE Select	c.-257G>C		upstream_gene	N/A	NP_073616.7
	DDX31	NM_001322341.2		c.-334G>C		upstream_gene	N/A	NP_001309270.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX31	ENST00000480876.3	TSL:1	c.-257G>C		5_prime_UTR	Exon 1 of 7	ENSP00000479697.2	Q9H8H2-6
	DDX31	ENST00000919393.1		c.-257G>C		5_prime_UTR	Exon 1 of 19	ENSP00000589452.1
	DDX31	ENST00000310532.7	TSL:2	c.-257G>C		5_prime_UTR	Exon 1 of 15	ENSP00000310539.2	A0AAK2PNZ4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.099
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.9
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0026	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.35
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.0060
Sift	Benign	0.11	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.11
MutPred		0.23		Loss of MoRF binding (P = 0.04)
MVP		0.41
MPC		0.43
ClinPred		0.42	T
GERP RS		0.56
PromoterAI		-0.084	Neutral
Varity_R		0.12
gMVP		0.073

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: chr9-135545578;