rs891187

Variant names:

• chr19-55160006-C-G
• rs891187
• NM_001256715.2:c.1056G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-55160006-C-G
• chr19-55160006-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001256715.2(DNAAF3):​c.1056G>C​(p.Pro352Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000763 in 1,310,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. P352P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: DNAAF3 NM_001256715.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.22
• Publications: 34 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]

ENSG00000267110 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.132).
• BP6: Variant 19-55160006-C-G is Benign according to our data. Variant chr19-55160006-C-G is described in ClinVar as Benign. ClinVar VariationId is 257681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.22 with no splicing effect.

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.1056G>C	p.Pro352Pro	synonymous	Exon 10 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.1257G>C	p.Pro419Pro	synonymous	Exon 10 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.1197G>C	p.Pro399Pro	synonymous	Exon 10 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.1056G>C	p.Pro352Pro	synonymous	Exon 10 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.894G>C	p.Pro298Pro	synonymous	Exon 10 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.*844G>C		non_coding_transcript_exon	Exon 10 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.0000405 AC: 6 AN: 148022 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000123

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: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 4 AN: 1162596 Hom.: 0 Cov.: 31 AF XY: 0.00000342 AC XY: 2 AN XY: 584944

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000128 AC: 4 AN: 31146

American (AMR) AF: 0.00 AC: 0 AN: 40934

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20792

East Asian (EAS) AF: 0.00 AC: 0 AN: 29644

South Asian (SAS) AF: 0.00 AC: 0 AN: 82252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 862772

Other (OTH) AF: 0.00 AC: 0 AN: 47650

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000405 AC: 6 AN: 148022 Hom.: 0 Cov.: 30 AF XY: 0.0000416 AC XY: 3 AN XY: 72082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000123 AC: 5 AN: 40522

American (AMR) AF: 0.00 AC: 0 AN: 14788

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.00 AC: 0 AN: 4750

South Asian (SAS) AF: 0.00 AC: 0 AN: 4466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9780

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

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67022

Other (OTH) AF: 0.00 AC: 0 AN: 2056

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 11895

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.68
DANN	Benign	0.51
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs891187; hg19: chr19-55671374;