rs599277

Variant names:

• chr11-73969018-G-A
• rs599277
• NM_153614.4:c.721-228G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-73969018-G-A
• chr11-73969018-G-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.721-228G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,930 control chromosomes in the GnomAD database, including 25,555 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (25555 hom., cov: 32)
• Consequence: DNAJB13 NM_153614.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.179
• Publications: 8 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=-0.87).
• BP6: Variant 11-73969018-G-A is Benign according to our data. Variant chr11-73969018-G-A is described in ClinVar as Benign. ClinVar VariationId is 1231202.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB13	NM_153614.4	MANE Select	c.721-228G>A		intron	N/A	NP_705842.2
	DNAJB13	NM_001441321.1		c.559-228G>A		intron	N/A	NP_001428250.1
	DNAJB13	NM_001377263.1		c.547-228G>A		intron	N/A	NP_001364192.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB13	ENST00000339764.6	TSL:1 MANE Select	c.721-228G>A		intron	N/A	ENSP00000344431.1
	DNAJB13	ENST00000543947.1	TSL:1	c.196-228G>A		intron	N/A	ENSP00000438576.1
	DNAJB13	ENST00000542350.5	TSL:3	c.421-228G>A		intron	N/A	ENSP00000440778.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84695 AN: 151812 Hom.: 25535 Cov.: 32

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.558 AC: 84760 AN: 151930 Hom.: 25555 Cov.: 32 AF XY: 0.555 AC XY: 41180 AN XY: 74254

African (AFR) AF: 0.814 AC: 33732 AN: 41462

American (AMR) AF: 0.525 AC: 8013 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1542 AN: 3462

East Asian (EAS) AF: 0.429 AC: 2221 AN: 5176

South Asian (SAS) AF: 0.399 AC: 1918 AN: 4812

European-Finnish (FIN) AF: 0.495 AC: 5212 AN: 10526

Middle Eastern (MID) AF: 0.445 AC: 129 AN: 290

European-Non Finnish (NFE) AF: 0.449 AC: 30516 AN: 67916

Other (OTH) AF: 0.530 AC: 1118 AN: 2108

Alfa AF: 0.513 Hom.: 4564

Bravo AF: 0.573

Asia WGS AF: 0.437 AC: 1517 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.87
CADD	Benign	0.12
DANN	Benign	0.49
PhyloP100		-0.18
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: rs599277; hg19: chr11-73680063;