rs150362958

Variant names:

• chr19-55166408-G-A
• rs150362958
• NM_001256715.2:c.6C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55166408-G-A
• chr19-55166408-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001256715.2(DNAAF3):​c.6C>T​(p.Thr2Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,613,794 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (13 hom., cov: 32)
  • Exomes 𝑓: 0.012 (118 hom.)
• Consequence: DNAAF3 NM_001256715.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.661
• Publications: 2 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 19-55166408-G-A is Benign according to our data. Variant chr19-55166408-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 238684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.661 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00817 (1244/152248) while in subpopulation NFE AF = 0.0145 (985/68020). AF 95% confidence interval is 0.0137. There are 13 homozygotes in GnomAd4. There are 561 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR,AD gene

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.6C>T	p.Thr2Thr	synonymous	Exon 2 of 12	NP_001243644.1	Q8N9W5-1
	DNAAF3	NM_001256714.1		c.147C>T	p.Thr49Thr	synonymous	Exon 2 of 12	NP_001243643.1	Q8N9W5-3
	DNAAF3	NM_178837.4		c.147C>T	p.Thr49Thr	synonymous	Exon 2 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.6C>T	p.Thr2Thr	synonymous	Exon 2 of 12	ENSP00000432046.3	Q8N9W5-1
	DNAAF3	ENST00000455045.5	TSL:1	c.-233C>T		5_prime_UTR	Exon 2 of 12	ENSP00000394343.1	Q8N9W5-7
	DNAAF3	ENST00000528412.5	TSL:1	n.6C>T		non_coding_transcript_exon	Exon 2 of 12	ENSP00000433826.2	Q8N9W5-5

Frequencies

GnomAD3 genomes AF: 0.00818 AC: 1244 AN: 152130 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00234

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00789 AC: 1959 AN: 248134 AF XY: 0.00786

Gnomad AFR exome AF: 0.00194

Gnomad AMR exome AF: 0.00321

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00748

Gnomad NFE exome AF: 0.0131

Gnomad OTH exome AF: 0.00893

GnomAD4 exome AF: 0.0122 AC: 17818 AN: 1461546 Hom.: 118 Cov.: 33 AF XY: 0.0120 AC XY: 8733 AN XY: 727052

African (AFR) AF: 0.00182 AC: 61 AN: 33480

American (AMR) AF: 0.00367 AC: 164 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00241 AC: 63 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00406 AC: 350 AN: 86252

European-Finnish (FIN) AF: 0.00839 AC: 447 AN: 53246

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.0146 AC: 16185 AN: 1111862

Other (OTH) AF: 0.00881 AC: 532 AN: 60378

GnomAD4 genome AF: 0.00817 AC: 1244 AN: 152248 Hom.: 13 Cov.: 32 AF XY: 0.00754 AC XY: 561 AN XY: 74442

African (AFR) AF: 0.00233 AC: 97 AN: 41544

American (AMR) AF: 0.00464 AC: 71 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00291 AC: 14 AN: 4816

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0145 AC: 985 AN: 68020

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.0104 Hom.: 8

Bravo AF: 0.00784

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.0119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	Primary ciliary dyskinesia 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		0.66
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	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: rs150362958; hg19: chr19-55677776;