rs1554667007

Variant names:

• chr8-132572449-G-A
• rs1554667007
• NM_012472.6:c.1258C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-132572449-G-A
• chr8-132572449-G-C
• chr8-132572449-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012472.6(DNAAF11):​c.1258C>T​(p.Pro420Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,453,460 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. P420T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAAF11 NM_012472.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.26
• Publications: 0 publications found

Genes affected

DNAAF11 (HGNC:16725): (dynein axonemal assembly factor 11) The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22. [provided by RefSeq, Apr 2016]

DNAAF11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 19

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35413736).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012472.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF11	NM_012472.6	MANE Select	c.1258C>T	p.Pro420Ser	missense	Exon 12 of 12	NP_036604.2
	DNAAF11	NM_001321961.2		c.1198C>T	p.Pro400Ser	missense	Exon 11 of 11	NP_001308890.1
	DNAAF11	NM_001321962.2		c.1012C>T	p.Pro338Ser	missense	Exon 10 of 10	NP_001308891.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF11	ENST00000620350.5	TSL:1 MANE Select	c.1258C>T	p.Pro420Ser	missense	Exon 12 of 12	ENSP00000484634.1
	DNAAF11	ENST00000519595.5	TSL:1	c.1258C>T	p.Pro420Ser	missense	Exon 12 of 12	ENSP00000429791.1
	DNAAF11	ENST00000250173.5	TSL:1	c.*122C>T		3_prime_UTR	Exon 13 of 13	ENSP00000250173.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453460 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722998

African (AFR) AF: 0.00 AC: 0 AN: 33088

American (AMR) AF: 0.00 AC: 0 AN: 43760

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25832

East Asian (EAS) AF: 0.00 AC: 0 AN: 39316

South Asian (SAS) AF: 0.00 AC: 0 AN: 84638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1107948

Other (OTH) AF: 0.00 AC: 0 AN: 60000

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.088	T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		6.3
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.19
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.35
MutPred		0.20		Gain of phosphorylation at P420 (P = 0.0322)
MVP		0.55
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.31
gMVP		0.45
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1554667007; hg19: chr8-133584697;