NM_001256715.2:c.529G>T

Variant names:

• chr19-55161777-C-A
• rs58824375
• NM_001256715.2:c.529G>T

Variant summary

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

The NM_001256715.2(DNAAF3):​c.529G>T​(p.Gly177Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000742 in 1,348,352 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. G177S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: DNAAF3 NM_001256715.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 0 publications found

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

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=0.18451378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAAF3	NM_001256715.2	c.529G>T	p.Gly177Cys	missense_variant	Exon 6 of 12	ENST00000524407.7	NP_001243644.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAAF3	ENST00000524407.7	c.529G>T	p.Gly177Cys	missense_variant	Exon 6 of 12	1	NM_001256715.2	ENSP00000432046.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.42e-7 AC: 1 AN: 1348352 Hom.: 0 Cov.: 33 AF XY: 0.00000151 AC XY: 1 AN XY: 661606

African (AFR) AF: 0.00 AC: 0 AN: 29850

American (AMR) AF: 0.00 AC: 0 AN: 29584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22666

East Asian (EAS) AF: 0.00 AC: 0 AN: 34892

South Asian (SAS) AF: 0.00 AC: 0 AN: 74042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38930

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 9.45e-7 AC: 1 AN: 1058418

Other (OTH) AF: 0.00 AC: 0 AN: 55836

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	.;T;.;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.47	T;T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	.;M;.;.
PhyloP100		0.064
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	D;.;.;N
REVEL	Benign	0.095
Sift	Benign	0.085	T;.;.;T
Sift4G	Benign	0.12	T;T;T;T
Polyphen		0.12	.;B;.;.
Vest4		0.25
MutPred		0.40		.;Loss of disorder (P = 0.0377);.;.;
MVP		0.17
MPC		1.7
ClinPred		0.76	D
GERP RS		2.5
Varity_R		0.14
gMVP		0.69
Mutation Taster		=86/14	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs58824375; hg19: chr19-55673145;