rs201937522

Variant names:

• chr19-55161315-G-A
• rs201937522
• NM_001256715.2:c.767C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55161315-G-A
• chr19-55161315-G-C

Variant summary

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

The NM_001256715.2(DNAAF3):​c.767C>T​(p.Ala256Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000621 in 1,610,506 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A256G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAAF3 NM_001256715.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08
• Publications: 1 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256715.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	NM_001256715.2	MANE Select	c.767C>T	p.Ala256Val	missense	Exon 7 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.971C>T	p.Ala324Val	missense	Exon 7 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.908C>T	p.Ala303Val	missense	Exon 7 of 12	NP_849159.2	Q8N9W5-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF3	ENST00000524407.7	TSL:1 MANE Select	c.767C>T	p.Ala256Val	missense	Exon 7 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.605C>T	p.Ala202Val	missense	Exon 7 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*555C>T		non_coding_transcript_exon	Exon 7 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.0000527 AC: 8 AN: 151808 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 242054 AF XY: 0.00

Gnomad AFR exome AF: 0.000204

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458698 Hom.: 0 Cov.: 39 AF XY: 0.00 AC XY: 0 AN XY: 725428

African (AFR) AF: 0.0000599 AC: 2 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 44360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 86014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5556

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110544

Other (OTH) AF: 0.00 AC: 0 AN: 60184

GnomAD4 genome AF: 0.0000527 AC: 8 AN: 151808 Hom.: 0 Cov.: 30 AF XY: 0.0000540 AC XY: 4 AN XY: 74132

African (AFR) AF: 0.000193 AC: 8 AN: 41368

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5126

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67904

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.1
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.11
Sift	Benign	0.29	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.23		Gain of sheet (P = 0.0827)
MVP		0.28
MPC		0.84
ClinPred		0.65	D
GERP RS		4.2
Varity_R		0.095
gMVP		0.68
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs201937522; hg19: chr19-55672683;