11-73958000-G-C

Variant names:

• chr11-73958000-G-C
• rs612914
• NM_153614.4:c.69-317G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153614.4(DNAJB13):​c.69-317G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 152,036 control chromosomes in the GnomAD database, including 21,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.53 (21834 hom., cov: 32)
• Consequence: DNAJB13 NM_153614.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.19
• Publications: 4 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, PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 11-73958000-G-C is Benign according to our data. Variant chr11-73958000-G-C is described in ClinVar as [Benign]. Clinvar id is 1235737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB13	NM_153614.4	c.69-317G>C		intron_variant	Intron 1 of 7	ENST00000339764.6	NP_705842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB13	ENST00000339764.6	c.69-317G>C		intron_variant	Intron 1 of 7	1	NM_153614.4	ENSP00000344431.1
DNAJB13	ENST00000535730.1	n.113-317G>C		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79779 AN: 151918 Hom.: 21815 Cov.: 32

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.468

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.525 AC: 79841 AN: 152036 Hom.: 21834 Cov.: 32 AF XY: 0.524 AC XY: 38918 AN XY: 74308

African (AFR) AF: 0.693 AC: 28749 AN: 41462

American (AMR) AF: 0.438 AC: 6695 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1593 AN: 3464

East Asian (EAS) AF: 0.485 AC: 2502 AN: 5160

South Asian (SAS) AF: 0.527 AC: 2545 AN: 4826

European-Finnish (FIN) AF: 0.468 AC: 4961 AN: 10590

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.458 AC: 31133 AN: 67952

Other (OTH) AF: 0.511 AC: 1077 AN: 2108

Alfa AF: 0.337 Hom.: 816

Bravo AF: 0.528

Asia WGS AF: 0.526 AC: 1829 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.43
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs612914; hg19: chr11-73669045; COSMIC: COSV60268925;