chr11-73951318-A-G

Variant names:

• chr11-73951318-A-G
• rs9666440
• NM_153614.4:c.68+181A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153614.4(DNAJB13):​c.68+181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,116 control chromosomes in the GnomAD database, including 1,452 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.13 (1452 hom., cov: 32)
• Consequence: DNAJB13 NM_153614.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.124
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-73951318-A-G is Benign according to our data. Variant chr11-73951318-A-G is described in ClinVar as [Benign]. Clinvar id is 1247658.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB13	NM_153614.4	c.68+181A>G		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.68+181A>G		intron_variant	Intron 1 of 7	1	NM_153614.4	ENSP00000344431.1
DNAJB13	ENST00000535730.1	n.112+181A>G		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20060 AN: 151998 Hom.: 1452 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.0791

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.132 AC: 20072 AN: 152116 Hom.: 1452 Cov.: 32 AF XY: 0.131 AC XY: 9708 AN XY: 74366

African (AFR) AF: 0.128 AC: 5303 AN: 41480

American (AMR) AF: 0.153 AC: 2342 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0832 AC: 289 AN: 3472

East Asian (EAS) AF: 0.0793 AC: 410 AN: 5172

South Asian (SAS) AF: 0.0504 AC: 243 AN: 4826

European-Finnish (FIN) AF: 0.180 AC: 1907 AN: 10584

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9149 AN: 67984

Other (OTH) AF: 0.131 AC: 277 AN: 2112

Alfa AF: 0.130 Hom.: 181

Bravo AF: 0.134

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 04, 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	-0.89
CADD	Benign	3.6
DANN	Benign	0.74
PhyloP100		0.12
PromoterAI		-0.022	Neutral
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: rs9666440; hg19: chr11-73662363;