rs599277

Positions:

• chr11-73969018-G-A
• chr11-73969018-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAJB13	NM_153614.4	c.721-228G>A		intron_variant		ENST00000339764.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAJB13	ENST00000339764.6	c.721-228G>A		intron_variant		1	NM_153614.4	P1
DNAJB13	ENST00000543947.1	c.196-228G>A		intron_variant		1
DNAJB13	ENST00000537753.5	c.196-228G>A		intron_variant		3
DNAJB13	ENST00000542350.5	c.422-228G>A		intron_variant		3

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

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.530

Alfa AF: 0.513 Hom.: 4564

Bravo AF: 0.573

Asia WGS AF: 0.437 AC: 1517 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs599277; hg19: chr11-73680063;