rs200165099

Variant names:

• chr12-124948170-C-A
• rs200165099
• NM_032656.4:c.3302G>T

Your query was ambiguous. Multiple possible variants found:

• chr12-124948170-C-A
• chr12-124948170-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_032656.4(DHX37):​c.3302G>T​(p.Arg1101Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1101C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: DHX37 NM_032656.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.74
• Publications: 0 publications found

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]

DHX37 Gene-Disease associations (from GenCC):

• 46,XY sex reversal 11

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• neurodevelopmental disorder with brain anomalies and with or without vertebral or cardiac anomalies

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 46,XY complete gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• 46,XY partial gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• testicular regression syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000301157 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.835

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032656.4. 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
	DHX37	NM_032656.4	MANE Select	c.3302G>T	p.Arg1101Leu	missense	Exon 26 of 27	NP_116045.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX37	ENST00000308736.7	TSL:1 MANE Select	c.3302G>T	p.Arg1101Leu	missense	Exon 26 of 27	ENSP00000311135.2	Q8IY37
	DHX37	ENST00000544745.2	TSL:1	c.2771G>T	p.Arg924Leu	missense	Exon 23 of 23	ENSP00000439009.2	F5H3Y4
	DHX37	ENST00000507267.2	TSL:1	n.446G>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		6.7
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-6.5	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.90
MutPred		0.54		Loss of MoRF binding (P = 0.0084)
MVP		0.67
MPC		0.66
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.73
gMVP		0.81
Mutation Taster		=32/68	disease causing

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: rs200165099; hg19: chr12-125432716;