chr12-124947886-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2

The NM_032656.4(DHX37):​c.3390C>A​(p.Tyr1130*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

DHX37
NM_032656.4 stop_gained, splice_region

Scores

2
4
1
Splicing: ADA: 0.06555
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.950
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0242 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DHX37NM_032656.4 linkc.3390C>A p.Tyr1130* stop_gained, splice_region_variant 27/27 ENST00000308736.7 NP_116045.2 Q8IY37
DHX37XM_005253590.4 linkc.*58C>A downstream_gene_variant XP_005253647.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DHX37ENST00000308736.7 linkc.3390C>A p.Tyr1130* stop_gained, splice_region_variant 27/271 NM_032656.4 ENSP00000311135.2 Q8IY37
DHX37ENST00000544745 linkc.*58C>A 3_prime_UTR_variant 23/231 ENSP00000439009.2 F5H3Y4
DHX37ENST00000507267.2 linkn.534C>A splice_region_variant, non_coding_transcript_exon_variant 2/21
DHX37ENST00000542400.5 linkn.2004C>A splice_region_variant, non_coding_transcript_exon_variant 6/62

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMar 28, 2023Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation as the last 28 amino acids are lost; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.54
D
BayesDel_noAF
Pathogenic
0.54
CADD
Pathogenic
43
DANN
Uncertain
1.0
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.95
D
Vest4
0.12
GERP RS
3.1

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.066
dbscSNV1_RF
Benign
0.45
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: chr12-125432432; API