NM_031427.4:c.4-67_4-56delACATACATACAT

Variant names:

• chr14-73654765-AATACATACATAC-A
• rs540475697
• NM_031427.4:c.4-67_4-56delACATACATACAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_031427.4(DNAL1):​c.4-67_4-56delACATACATACAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00296 in 1,287,512 control chromosomes in the GnomAD database, including 12 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0022 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0031 (10 hom.)
• Consequence: DNAL1 NM_031427.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.933

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00223 (338/151764) while in subpopulation AMR AF= 0.00544 (83/15250). AF 95% confidence interval is 0.0045. There are 2 homozygotes in gnomad4. There are 158 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.4-67_4-56delACATACATACAT		intron_variant	Intron 1 of 7	ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.-114-67_-114-56delACATACATACAT		intron_variant	Intron 2 of 8		NP_001188295.1
DNAL1	XM_017021679.3	c.-114-67_-114-56delACATACATACAT		intron_variant	Intron 2 of 8		XP_016877168.1
DNAL1	XM_024449715.2	c.-114-67_-114-56delACATACATACAT		intron_variant	Intron 2 of 8		XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.4-81_4-70delATACATACATAC		intron_variant	Intron 1 of 7	1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes AF: 0.00223 AC: 338 AN: 151658 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.000752

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00545

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00319

Gnomad OTH AF: 0.00240

GnomAD4 exome AF: 0.00305 AC: 3469 AN: 1135748 Hom.: 10 AF XY: 0.00304 AC XY: 1706 AN XY: 561812

Gnomad4 AFR exome AF: 0.000395

Gnomad4 AMR exome AF: 0.00298

Gnomad4 ASJ exome AF: 0.000511

Gnomad4 EAS exome AF: 0.0000309

Gnomad4 SAS exome AF: 0.0000672

Gnomad4 FIN exome AF: 0.000160

Gnomad4 NFE exome AF: 0.00358

Gnomad4 OTH exome AF: 0.00328

GnomAD4 genome AF: 0.00223 AC: 338 AN: 151764 Hom.: 2 Cov.: 31 AF XY: 0.00213 AC XY: 158 AN XY: 74168

Gnomad4 AFR AF: 0.000750

Gnomad4 AMR AF: 0.00544

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000953

Gnomad4 NFE AF: 0.00319

Gnomad4 OTH AF: 0.00238

Alfa AF: 0.00128 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs540475697; hg19: chr14-74121468;