rs754776389

Variant names:

• chr11-73969996-T-A
• NM_153614.4:c.833T>A

Your query was ambiguous. Multiple possible variants found:

• chr11-73969996-T-A
• chr11-73969996-T-C
• chr11-73969996-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_153614.4(DNAJB13):​c.833T>A​(p.Met278Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAJB13 NM_153614.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.03

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]

ENSG00000255847 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAJB13	NM_153614.4	c.833T>A	p.Met278Lys	missense_variant	Exon 8 of 8	ENST00000339764.6	NP_705842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAJB13	ENST00000339764.6	c.833T>A	p.Met278Lys	missense_variant	Exon 8 of 8	1	NM_153614.4	ENSP00000344431.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459400 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725820

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T;.;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.95	D;D;D
MetaSVM	Uncertain	0.043	D
MutationAssessor	Pathogenic	4.5	H;.;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Pathogenic	0.67
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.92
MutPred		0.83		Gain of ubiquitination at M278 (P = 0.03);.;.;
MVP		0.70
MPC		1.1
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.93
gMVP		0.97

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-73681041;