chr17-59598833-T-A

Position:

• chr17-59598833-T-A

Variant summary

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

The NM_024612.5(DHX40):​c.1679T>A​(p.Phe560Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DHX40 NM_024612.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18

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]

DHX40 (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	Protein	UniProt
DHX40	NM_024612.5	c.1679T>A	p.Phe560Tyr	missense_variant	13/18	ENST00000251241.9	NP_078888.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX40	ENST00000251241.9	c.1679T>A	p.Phe560Tyr	missense_variant	13/18	1	NM_024612.5	ENSP00000251241.4
DHX40	ENST00000425628.7	c.1448T>A	p.Phe483Tyr	missense_variant	12/17	2		ENSP00000388749.3
DHX40	ENST00000538926.2	c.623T>A	p.Phe208Tyr	missense_variant	5/6	3		ENSP00000437958.2
DHX40	ENST00000583439.1	n.230T>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 910764 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 475668

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2021

The c.1679T>A (p.F560Y) alteration is located in exon 13 (coding exon 13) of the DHX40 gene. This alteration results from a T to A substitution at nucleotide position 1679, causing the phenylalanine (F) at amino acid position 560 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Benign	0.85
DEOGEN2	Benign	0.073	T;.
Eigen	Benign	0.061
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	0.39	N;.
REVEL	Benign	0.23
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.23	B;.
Vest4		0.64
MutPred		0.68		Loss of ubiquitination at K564 (P = 0.1016);.;
MVP		0.50
MPC		2.2
ClinPred		0.84	D
GERP RS		5.6
Varity_R		0.21
gMVP		0.59

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-57676194;