11-73951088-T-C

Variant names:

• chr11-73951088-T-C
• rs202023755
• NM_153614.4:c.19T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153614.4(DNAJB13):​c.19T>C​(p.Ser7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S7T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAJB13 NM_153614.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15862644).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB13	NM_153614.4	c.19T>C	p.Ser7Pro	missense_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.19T>C	p.Ser7Pro	missense_variant	Exon 1 of 8	1	NM_153614.4	ENSP00000344431.1
DNAJB13	ENST00000535730.1	n.63T>C		non_coding_transcript_exon_variant	Exon 1 of 3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461760 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727176

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.093	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.64
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.043	D
Polyphen		0.025	B
Vest4		0.33
MutPred		0.51		Loss of phosphorylation at Y6 (P = 0.077);
MVP		0.47
MPC		0.35
ClinPred		0.40	T
GERP RS		-6.0
PromoterAI		-0.039	Neutral
Varity_R		0.43
gMVP		0.57
Mutation Taster		=81/19	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: rs202023755; hg19: chr11-73662133;