NM_014003.4:c.3600-16C>T

Variant names:

• chr16-72112397-C-T
• rs374773050
• NM_014003.4:c.3600-16C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014003.4(DHX38):​c.3600-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,575,754 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000058 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: DHX38 NM_014003.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.360
• Publications: 0 publications found

Genes affected

DHX38 (HGNC:17211): (DEAH-box helicase 38) 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. The protein encoded by this gene is a member of the DEAD/H box family of splicing factors. This protein resembles yeast Prp16 more closely than other DEAD/H family members. It is an ATPase and essential for the catalytic step II in pre-mRNA splicing process. [provided by RefSeq, Jul 2008]

PMFBP1 (HGNC:17728): (polyamine modulated factor 1 binding protein 1) Involved in spermatogenesis. Located in sperm connecting piece. Implicated in spermatogenic failure 31. [provided by Alliance of Genome Resources, Apr 2022]

PMFBP1 Gene-Disease associations (from GenCC):

• spermatogenic failure 31

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-72112397-C-T is Benign according to our data. Variant chr16-72112397-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1654698.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014003.4. 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
	DHX38	NM_014003.4	MANE Select	c.3600-16C>T		intron	N/A	NP_054722.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHX38	ENST00000268482.8	TSL:1 MANE Select	c.3600-16C>T		intron	N/A	ENSP00000268482.3	Q92620-1
	PMFBP1	ENST00000537792.6	TSL:2	c.*364G>A		3_prime_UTR	Exon 20 of 20	ENSP00000443366.2
	DHX38	ENST00000904787.1		c.3678-16C>T		intron	N/A	ENSP00000574846.1

Frequencies

GnomAD3 genomes AF: 0.0000575 AC: 7 AN: 121672 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000128

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 244176 AF XY: 0.0000226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000227 AC: 33 AN: 1454082 Hom.: 0 Cov.: 30 AF XY: 0.0000207 AC XY: 15 AN XY: 723688

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.0000434 AC: 2 AN: 46084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.0000261 AC: 29 AN: 1111664

Other (OTH) AF: 0.0000166 AC: 1 AN: 60332

GnomAD4 genome AF: 0.0000575 AC: 7 AN: 121672 Hom.: 0 Cov.: 31 AF XY: 0.0000334 AC XY: 2 AN XY: 59852

African (AFR) AF: 0.00 AC: 0 AN: 31962

American (AMR) AF: 0.00 AC: 0 AN: 12142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2812

East Asian (EAS) AF: 0.00 AC: 0 AN: 4186

South Asian (SAS) AF: 0.00 AC: 0 AN: 3836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.000128 AC: 7 AN: 54770

Other (OTH) AF: 0.00 AC: 0 AN: 1628

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.77
PhyloP100		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs374773050; hg19: chr16-72146296;