2-38802858-C-A

Variant names:

• chr2-38802858-C-A
• rs748146523
• NM_198963.3:c.3874G>T

Variant summary

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

The NM_198963.3(DHX57):​c.3874G>T​(p.Val1292Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V1292I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DHX57 NM_198963.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95
• Publications: 0 publications found

Genes affected

DHX57 (HGNC:20086): (DExH-box helicase 57) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

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_198963.3. 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
	DHX57	NM_198963.3	MANE Select	c.3874G>T	p.Val1292Leu	missense	Exon 23 of 24	NP_945314.1	Q6P158-1
	DHX57	NM_001329963.1		c.3568G>T	p.Val1190Leu	missense	Exon 23 of 24	NP_001316892.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX57	ENST00000457308.6	TSL:1 MANE Select	c.3874G>T	p.Val1292Leu	missense	Exon 23 of 24	ENSP00000405111.2	Q6P158-1
	DHX57	ENST00000620517.4	TSL:1	n.*2172G>T		non_coding_transcript_exon	Exon 22 of 23	ENSP00000482275.1	A0A087WZ11
	DHX57	ENST00000622155.4	TSL:1	n.4901G>T		non_coding_transcript_exon	Exon 22 of 23

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.046	T
Eigen	Benign	0.058
Eigen_PC	Benign	0.043
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.0
PrimateAI	Pathogenic	0.79	T
Sift4G	Uncertain	0.026	D
Polyphen		0.95	P
Vest4		0.75
MutPred		0.51		Gain of catalytic residue at V1292 (P = 0.0567)
MVP		0.54
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.45
Mutation Taster		=72/28	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

dbSNP: rs748146523; hg19: chr2-39030000;