5-13770832-C-T

Variant names:

• chr5-13770832-C-T
• rs35233147
• NM_001369.3:c.9522G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001369.3(DNAH5):​c.9522G>A​(p.Thr3174Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00477 in 1,613,966 control chromosomes in the GnomAD database, including 253 homozygotes. 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. T3174T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.023 (119 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (134 hom.)
• Consequence: DNAH5 NM_001369.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -5.22
• Publications: 3 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: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 5-13770832-C-T is Benign according to our data. Variant chr5-13770832-C-T is described in ClinVar as Benign. ClinVar VariationId is 226607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-5.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	NM_001369.3	MANE Select	c.9522G>A	p.Thr3174Thr	synonymous	Exon 56 of 79	NP_001360.1	Q8TE73

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH5	ENST00000265104.5	TSL:1 MANE Select	c.9522G>A	p.Thr3174Thr	synonymous	Exon 56 of 79	ENSP00000265104.4	Q8TE73
	DNAH5	ENST00000681290.1		c.9477G>A	p.Thr3159Thr	synonymous	Exon 56 of 79	ENSP00000505288.1	A0A7P0Z455
	DNAH5	ENST00000504001.3	TSL:5	n.234G>A		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.0228 AC: 3471 AN: 152052 Hom.: 119 Cov.: 33

Gnomad AFR AF: 0.0786

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0148

GnomAD2 exomes AF: 0.00616 AC: 1548 AN: 251178 AF XY: 0.00483

Gnomad AFR exome AF: 0.0789

Gnomad AMR exome AF: 0.00423

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000687

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00289 AC: 4230 AN: 1461796 Hom.: 134 Cov.: 31 AF XY: 0.00260 AC XY: 1890 AN XY: 727200

African (AFR) AF: 0.0852 AC: 2852 AN: 33470

American (AMR) AF: 0.00497 AC: 222 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000417 AC: 36 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00937 AC: 54 AN: 5766

European-Non Finnish (NFE) AF: 0.000634 AC: 705 AN: 1111964

Other (OTH) AF: 0.00583 AC: 352 AN: 60390

GnomAD4 genome AF: 0.0228 AC: 3476 AN: 152170 Hom.: 119 Cov.: 33 AF XY: 0.0218 AC XY: 1625 AN XY: 74398

African (AFR) AF: 0.0785 AC: 3260 AN: 41504

American (AMR) AF: 0.00910 AC: 139 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68006

Other (OTH) AF: 0.0147 AC: 31 AN: 2114

Alfa AF: 0.0140 Hom.: 45

Bravo AF: 0.0262

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.000600

EpiControl AF: 0.00119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.022
DANN	Benign	0.72
PhyloP100		-5.2
Mutation Taster		=89/11	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs35233147; hg19: chr5-13770941;