rs779613772

chr12-124967167-C-Achr12-124967167-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_032656.4(DHX37):c.1460G>T(p.Arg487Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,430 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. R487H) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DHX37 NM_032656.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80

Genes affected

DHX37 (HGNC:17210): (DEAH-box helicase 37) This gene encodes a DEAD box protein. DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr12-124967167-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 402138.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=1, Uncertain_significance=2}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHX37	NM_032656.4	c.1460G>T	p.Arg487Leu	missense_variant	11/27	ENST00000308736.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHX37	ENST00000308736.7	c.1460G>T	p.Arg487Leu	missense_variant	11/27	1	NM_032656.4	P1
DHX37	ENST00000544745.2	c.932G>T	p.Arg311Leu	missense_variant	8/23	1
DHX37	ENST00000679875.1	n.1532G>T		non_coding_transcript_exon_variant	11/18

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461430 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727046

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.22	T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.3	D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.77	P;.
Vest4		0.68
MutPred		0.42		Loss of MoRF binding (P = 0.0067);.;
MVP		0.56
MPC		0.86
ClinPred		0.96	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.63
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs779613772; hg19: chr12-125451713;