3-154284651-C-T

Variant names:

• chr3-154284651-C-T
• rs1432551622
• NM_020865.3:c.2224G>A

Variant summary

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

The NM_020865.3(DHX36):​c.2224G>A​(p.Asp742Asn) variant causes a missense change involving the alteration of a conserved nucleotide. 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: DHX36 NM_020865.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.66
• Publications: 0 publications found

Genes affected

DHX36 (HGNC:14410): (DEAH-box helicase 36) This gene is a member of the DEAH-box family of RNA-dependent NTPases which are named after the conserved amino acid sequence Asp-Glu-Ala-His in motif II. The protein encoded by this gene has been shown to enhance the deadenylation and decay of mRNAs with 3'-UTR AU-rich elements (ARE-mRNA). The protein has also been shown to resolve into single strands the highly stable tetramolecular DNA configuration (G4) that can form spontaneously in guanine-rich regions of DNA. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020865.3. 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
	DHX36	NM_020865.3	MANE Select	c.2224G>A	p.Asp742Asn	missense	Exon 19 of 25	NP_065916.2	Q9H2U1-1
	DHX36	NM_001114397.2		c.2182G>A	p.Asp728Asn	missense	Exon 19 of 25	NP_001107869.1	Q9H2U1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX36	ENST00000496811.6	TSL:1 MANE Select	c.2224G>A	p.Asp742Asn	missense	Exon 19 of 25	ENSP00000417078.1	Q9H2U1-1
	DHX36	ENST00000329463.9	TSL:1	c.2182G>A	p.Asp728Asn	missense	Exon 19 of 25	ENSP00000330113.5	Q9H2U1-2
	DHX36	ENST00000308361.10	TSL:1	c.2205+163G>A		intron	N/A	ENSP00000309296.6	Q9H2U1-3

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	Pathogenic	0.78
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.7
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.17
Sift	Benign	0.39	T
Sift4G	Benign	0.61	T
Polyphen		0.38	B
Vest4		0.60
MutPred		0.51		Loss of ubiquitination at K737 (P = 0.0433)
MVP		0.61
MPC		0.84
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.27
gMVP		0.57
Mutation Taster		=19/81	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs1432551622; hg19: chr3-154002440;