19-55160687-A-T

Variant names:

• chr19-55160687-A-T
• NM_001256715.2:c.1001T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001256715.2(DNAAF3):​c.1001T>A​(p.Leu334Gln) 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 1,461,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. L334P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAAF3 NM_001256715.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.170

Genes affected

DNAAF3 (HGNC:30492): (dynein axonemal assembly factor 3) The protein encoded by this gene is required for the assembly of axonemal inner and outer dynein arms and plays a role in assembling dynein complexes for transport into cilia. Defects in this gene are a cause of primary ciliary dyskinesia type 2 (CILD2). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2012]

DNAAF3-AS1 (HGNC:55292): (DNAAF3 antisense RNA 1)

ENSG00000267110 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054259688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2	c.1001T>A	p.Leu334Gln	missense_variant	Exon 9 of 12	ENST00000524407.7	NP_001243644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7	c.1001T>A	p.Leu334Gln	missense_variant	Exon 9 of 12	1	NM_001256715.2	ENSP00000432046.3
ENSG00000267110	ENST00000587871.1	n.-17T>A		upstream_gene_variant		5		ENSP00000473050.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461484 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727074

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Benign	0.062
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.7
DANN	Benign	0.83
DEOGEN2	Benign	0.0012	.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.23	T;T;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.054	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	.;N;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.97	N;.;.;N
REVEL	Benign	0.13
Sift	Benign	0.54	T;.;.;T
Sift4G	Benign	0.32	T;T;T;T
Polyphen		0.027	.;B;.;.
Vest4		0.14
MutPred		0.20		.;Gain of solvent accessibility (P = 0.0216);.;.;
MVP		0.072
MPC		0.27
ClinPred		0.057	T
GERP RS		1.5
Varity_R		0.046
gMVP		0.40

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: chr19-55672055;