chr11-73969996-TG-AA

Variant names:

• chr11-73969996-TG-AA
• NM_153614.4:c.833_834delTGinsAA
• DNAJB13 p.Met278Lys

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM5 PP3

The NM_153614.4(DNAJB13):​c.833_834delTGinsAA​(p.Met278Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. M278R) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DNAJB13 NM_153614.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.77
• Publications: 0 publications found

Genes affected

DNAJB13 (HGNC:30718): (DnaJ heat shock protein family (Hsp40) member B13) This gene encodes a member of the heat shock protein 40 co-chaperone family which is produced in large amounts in the testis and is located on the radial spokes of the axoneme in human sperm flagella and other flagellar structures. The encoded protein associates with the sperm annulus, as part of the septin complex, through direct interaction with septin 4, during sperm terminal differentiation. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and male infertility. [provided by RefSeq, Apr 2017]

DNAJB13 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 34

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• PM5: Other missense variant is known to change same aminoacid residue: Variant chr11-73969996-T-G is described in ClinVar as Pathogenic. ClinVar VariationId is 253328.Status of the report is no_assertion_criteria_provided, 0 stars.
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153614.4. 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
	DNAJB13	NM_153614.4	MANE Select	c.833_834delTGinsAA	p.Met278Lys	missense	N/A	NP_705842.2
	DNAJB13	NM_001441321.1		c.671_672delTGinsAA	p.Met224Lys	missense	N/A	NP_001428250.1
	DNAJB13	NM_001377263.1		c.659_660delTGinsAA	p.Met220Lys	missense	N/A	NP_001364192.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB13	ENST00000339764.6	TSL:1 MANE Select	c.833_834delTGinsAA	p.Met278Lys	missense	N/A	ENSP00000344431.1	P59910-1
	DNAJB13	ENST00000543947.1	TSL:1	c.308_309delTGinsAA	p.Met103Lys	missense	N/A	ENSP00000438576.1	P59910-2
	DNAJB13	ENST00000897971.1		c.671_672delTGinsAA	p.Met224Lys	missense	N/A	ENSP00000568030.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-73681041;