14-73689398-C-T

Variant names:

• chr14-73689398-C-T
• rs141873943
• NM_031427.4:c.415C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_031427.4(DNAL1):​c.415C>T​(p.Leu139Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,750 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.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: DNAL1 NM_031427.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• Publications: 6 publications found

Genes affected

DNAL1 (HGNC:23247): (dynein axonemal light chain 1) This gene encodes an axonemal dynein light chain which functions as a component of the outer dynein arms complex. This complex acts as the molecular motor that provides the force to move cilia in an ATP-dependent manner. The encoded protein is expressed in tissues with motile cilia or flagella and may be involved in the movement of sperm flagella. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jan 2011]

DNAL1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 16

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=0.269 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031427.4. 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
	DNAL1	NM_031427.4	MANE Select	c.415C>T	p.Leu139Leu	synonymous	Exon 7 of 8	NP_113615.2
	DNAL1	NM_001201366.2		c.298C>T	p.Leu100Leu	synonymous	Exon 8 of 9	NP_001188295.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAL1	ENST00000553645.7	TSL:1 MANE Select	c.415C>T	p.Leu139Leu	synonymous	Exon 7 of 8	ENSP00000452037.1
	DNAL1	ENST00000554871.5	TSL:1	c.298C>T	p.Leu100Leu	synonymous	Exon 8 of 9	ENSP00000451834.1
	DNAL1	ENST00000555631.6	TSL:4	c.298C>T	p.Leu100Leu	synonymous	Exon 8 of 8	ENSP00000451547.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400750 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690976

African (AFR) AF: 0.00 AC: 0 AN: 31652

American (AMR) AF: 0.00 AC: 0 AN: 35732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35862

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079574

Other (OTH) AF: 0.00 AC: 0 AN: 58174

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.1
DANN	Benign	0.73
PhyloP100		0.27

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: rs141873943; hg19: chr14-74156101;