chr6-31540401-G-C

Position:

• chr6-31540401-G-C

Variant summary

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

The NM_004640.7(DDX39B):​c.132C>G​(p.Ser44Arg) 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: DDX39B NM_004640.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21

Genes affected

DDX39B (HGNC:13917): (DExD-box helicase 39B) This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B (HGNC:):

ACMG classification

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
DDX39B	NM_004640.7	c.132C>G	p.Ser44Arg	missense_variant	2/11	ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.935C>G		non_coding_transcript_exon_variant	4/13
DDX39B	NM_080598.6	c.132C>G	p.Ser44Arg	missense_variant	2/11
DDX39B	NR_037852.2	n.318C>G		non_coding_transcript_exon_variant	2/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.132C>G	p.Ser44Arg	missense_variant	2/11	1	NM_004640.7	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neurodevelopmental disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Undiagnosed Rare Disease Clinic, Indiana University School of Medicine

Mar 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.021	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.85	T
MutationTaster	Benign	1.0	D;D;D;D;D;N;N
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.24
Sift	Benign	0.044	D
MutPred		0.70		Loss of catalytic residue at M35 (P = 0.0869);
MVP		0.64
ClinPred		0.99	D
GERP RS		4.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: 0

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: chr6-31508178;