11-73951054-T-G

Variant names:

• chr11-73951054-T-G
• rs9666551
• NM_153614.4:c.-16T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153614.4(DNAJB13):​c.-16T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000699 in 1,613,810 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00038 (4 hom.)
• Consequence: DNAJB13 NM_153614.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.779
• 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, 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=-0.72).
• BP6: Variant 11-73951054-T-G is Benign according to our data. Variant chr11-73951054-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1317548.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00376 (573/152332) while in subpopulation AFR AF = 0.0131 (545/41578). AF 95% confidence interval is 0.0122. There are 0 homozygotes in GnomAd4. There are 274 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB13	NM_153614.4	c.-16T>G		5_prime_UTR_variant	Exon 1 of 8	ENST00000339764.6	NP_705842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB13	ENST00000339764.6	c.-16T>G		5_prime_UTR_variant	Exon 1 of 8	1	NM_153614.4	ENSP00000344431.1
DNAJB13	ENST00000535730.1	n.29T>G		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 573 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

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: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000954 AC: 239 AN: 250540 AF XY: 0.000738

Gnomad AFR exome AF: 0.0128

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000380 AC: 555 AN: 1461478 Hom.: 4 Cov.: 30 AF XY: 0.000342 AC XY: 249 AN XY: 727016

African (AFR) AF: 0.0134 AC: 450 AN: 33472

American (AMR) AF: 0.000761 AC: 34 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53222

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5764

European-Non Finnish (NFE) AF: 0.00000989 AC: 11 AN: 1111894

Other (OTH) AF: 0.000828 AC: 50 AN: 60388

GnomAD4 genome AF: 0.00376 AC: 573 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.00368 AC XY: 274 AN XY: 74494

African (AFR) AF: 0.0131 AC: 545 AN: 41578

American (AMR) AF: 0.00150 AC: 23 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.00179 Hom.: 0

Bravo AF: 0.00441

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 20, 2020

GeneDx

Significance: Likely 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	-0.72
CADD	Benign	5.7
DANN	Benign	0.84
PhyloP100		-0.78
PromoterAI		0.065	Neutral
Mutation Taster		=300/0	polymorphism

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: rs9666551; hg19: chr11-73662099;