rs112911055

Variant names:

• chr5-13914589-G-A
• rs112911055
• NM_001369.3:c.1251C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-13914589-G-A
• chr5-13914589-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS1

The NM_001369.3(DNAH5):​c.1251C>T​(p.Thr417Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,613,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0010 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000097 (0 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:4
• Conservation: PhyloP100: -0.768
• Publications: 1 publications found

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

DNAH5 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-13914589-G-A is Benign according to our data. Variant chr5-13914589-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 193629.
• BP7: Synonymous conserved (PhyloP=-0.768 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00103 (157/152108) while in subpopulation AFR AF = 0.00349 (145/41530). AF 95% confidence interval is 0.00303. There are 1 homozygotes in GnomAd4. There are 74 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369.3. 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
	DNAH5	NM_001369.3	MANE Select	c.1251C>T	p.Thr417Thr	synonymous	Exon 10 of 79	NP_001360.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.1251C>T	p.Thr417Thr	synonymous	Exon 10 of 79	ENSP00000265104.4
	DNAH5	ENST00000681290.1		c.1206C>T	p.Thr402Thr	synonymous	Exon 10 of 79	ENSP00000505288.1
	DNAH5	ENST00000508040.1	TSL:2	n.1659C>T		non_coding_transcript_exon	Exon 10 of 12

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 157 AN: 151990 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000283 AC: 71 AN: 250936 AF XY: 0.000206

Gnomad AFR exome AF: 0.00375

Gnomad AMR exome AF: 0.000202

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: 0.000490

GnomAD4 exome AF: 0.0000965 AC: 141 AN: 1461044 Hom.: 0 Cov.: 31 AF XY: 0.0000867 AC XY: 63 AN XY: 726836

African (AFR) AF: 0.00293 AC: 98 AN: 33452

American (AMR) AF: 0.000179 AC: 8 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39648

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5744

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111386

Other (OTH) AF: 0.000331 AC: 20 AN: 60358

GnomAD4 genome AF: 0.00103 AC: 157 AN: 152108 Hom.: 1 Cov.: 32 AF XY: 0.000995 AC XY: 74 AN XY: 74360

African (AFR) AF: 0.00349 AC: 145 AN: 41530

American (AMR) AF: 0.000459 AC: 7 AN: 15262

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67924

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000426 Hom.: 0

Bravo AF: 0.00118

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		-0.77
Mutation Taster		=89/11	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: rs112911055; hg19: chr5-13914698;