chr4-24540945-T-C

Variant names:

• chr4-24540945-T-C
• NM_001358.3:c.1489A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001358.3(DHX15):​c.1489A>G​(p.Asn497Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,282 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DHX15 NM_001358.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• Publications: 0 publications found

Genes affected

DHX15 (HGNC:2738): (DEAH-box helicase 15) The protein encoded by this gene is a putative ATP-dependent RNA helicase implicated in pre-mRNA splicing. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3532877).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358.3. 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
	DHX15	NM_001358.3	MANE Select	c.1489A>G	p.Asn497Asp	missense	Exon 9 of 14	NP_001349.2	O43143

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX15	ENST00000336812.5	TSL:1 MANE Select	c.1489A>G	p.Asn497Asp	missense	Exon 9 of 14	ENSP00000336741.4	O43143
	DHX15	ENST00000853185.1		c.1480A>G	p.Asn494Asp	missense	Exon 9 of 14	ENSP00000523244.1
	DHX15	ENST00000853187.1		c.1489A>G	p.Asn497Asp	missense	Exon 9 of 14	ENSP00000523246.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.99e-7 AC: 1 AN: 1431282 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 713080

African (AFR) AF: 0.00 AC: 0 AN: 32248

American (AMR) AF: 0.00 AC: 0 AN: 41428

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25352

East Asian (EAS) AF: 0.00 AC: 0 AN: 39318

South Asian (SAS) AF: 0.00 AC: 0 AN: 83134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 9.16e-7 AC: 1 AN: 1091684

Other (OTH) AF: 0.00 AC: 0 AN: 59268

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	0.85
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.94	L
PhyloP100		7.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.098
Sift	Benign	0.061	T
Sift4G	Benign	0.17	T
Polyphen		0.23	B
Vest4		0.67
MutPred		0.38		Gain of helix (P = 0.0696)
MVP		0.49
MPC		2.3
ClinPred		0.66	D
GERP RS		6.0
Varity_R		0.35
gMVP		0.97
Mutation Taster		=61/39	polymorphism

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: chr4-24542568;