rs770403610

Variant names:

• chr19-55162263-C-G
• NM_001256715.2:c.350G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-55162263-C-G
• chr19-55162263-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001256715.2(DNAAF3):​c.350G>C​(p.Trp117Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000091 in 1,098,392 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: DNAAF3 NM_001256715.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

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)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2	c.350G>C	p.Trp117Ser	missense_variant	Exon 5 of 12	ENST00000524407.7	NP_001243644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7	c.350G>C	p.Trp117Ser	missense_variant	Exon 5 of 12	1	NM_001256715.2	ENSP00000432046.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.10e-7 AC: 1 AN: 1098392 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 518756

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: 0.00000109

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Uncertain	0.49	.;T;.;.;D;D;.
Eigen	Benign	-0.051
Eigen_PC	Benign	-0.072
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.72	T;T;T;T;T;T;T
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	.;M;.;.;.;.;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-5.9	D;.;.;D;.;.;.
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D;.;.;D;.;.;.
Sift4G	Uncertain	0.014	D;D;D;D;D;.;.
Polyphen		0.87	.;P;.;.;.;.;.
Vest4		0.62
MutPred		0.74		.;Gain of disorder (P = 0.0035);.;.;Gain of disorder (P = 0.0035);.;.;
MVP		0.30
MPC		3.3
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.22
gMVP		0.77

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: chr19-55673631;