NM_024612.5:c.32C>G

Variant names:

• chr17-59565703-C-G
• rs200846551
• NM_024612.5:c.32C>G

Variant summary

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

The NM_024612.5(DHX40):​c.32C>G​(p.Ala11Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,450,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A11E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: DHX40 NM_024612.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.58
• Publications: 0 publications found

Genes affected

DHX40 (HGNC:18018): (DEAH-box helicase 40) This gene encodes a member of the DExH/D box family of ATP-dependent RNA helicases that have an essential role in RNA metabolism. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 17.[provided by RefSeq, Oct 2009]

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=0.16811103).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024612.5. 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
	DHX40	NM_024612.5	MANE Select	c.32C>G	p.Ala11Gly	missense	Exon 1 of 18	NP_078888.4
	DHX40	NM_001166301.2		c.32C>G	p.Ala11Gly	missense	Exon 1 of 17	NP_001159773.1	Q8IX18-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX40	ENST00000251241.9	TSL:1 MANE Select	c.32C>G	p.Ala11Gly	missense	Exon 1 of 18	ENSP00000251241.4	Q8IX18-1
	DHX40	ENST00000930678.1		c.32C>G	p.Ala11Gly	missense	Exon 1 of 19	ENSP00000600737.1
	DHX40	ENST00000930680.1		c.32C>G	p.Ala11Gly	missense	Exon 1 of 18	ENSP00000600739.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1450970 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722214

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43292

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111528

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Benign	0.047	T
Eigen	Benign	0.097
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.050
Sift	Uncertain	0.017	D
Sift4G	Benign	0.38	T
Polyphen		0.59	P
Vest4		0.31
MutPred		0.24		Loss of helix (P = 0.0304)
MVP		0.21
MPC		0.98
ClinPred		0.57	D
GERP RS		5.4
PromoterAI		0.029	Neutral
Varity_R		0.33
gMVP		0.28
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs200846551; hg19: chr17-57643064;