14-73654828-CT-C

Position:

• chr14-73654828-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_031427.4(DNAL1):​c.4-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 141,702 control chromosomes in the GnomAD database, including 42 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (42 hom., cov: 31)
  • Exomes 𝑓: 0.34 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAL1 NM_031427.4 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.663

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 -10 ACMG points.

• BP6: Variant 14-73654828-CT-C is Benign according to our data. Variant chr14-73654828-CT-C is described in ClinVar as [Benign]. Clinvar id is 1295016.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0171 (2424/141702) while in subpopulation AFR AF= 0.0415 (1616/38902). AF 95% confidence interval is 0.0399. There are 42 homozygotes in gnomad4. There are 1170 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.4-5delT		splice_region_variant, intron_variant		ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.-114-5delT		splice_region_variant, intron_variant			NP_001188295.1
DNAL1	XM_017021679.3	c.-114-5delT		splice_region_variant, intron_variant			XP_016877168.1
DNAL1	XM_024449715.2	c.-114-5delT		splice_region_variant, intron_variant			XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.4-5delT		splice_region_variant, intron_variant		1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2417 AN: 141688 Hom.: 41 Cov.: 31

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.0193

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00661

Gnomad EAS AF: 0.00141

Gnomad SAS AF: 0.000445

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.00993

Gnomad NFE AF: 0.00682

Gnomad OTH AF: 0.0133

GnomAD3 exomes AF: 0.401 AC: 29770 AN: 74314 Hom.: 3 AF XY: 0.414 AC XY: 16712 AN XY: 40328

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.434

Gnomad EAS exome AF: 0.409

Gnomad SAS exome AF: 0.446

Gnomad FIN exome AF: 0.353

Gnomad NFE exome AF: 0.390

Gnomad OTH exome AF: 0.409

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.338 AC: 292317 AN: 863578 Hom.: 2 Cov.: 0 AF XY: 0.340 AC XY: 145929 AN XY: 429308

Gnomad4 AFR exome AF: 0.342

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.353

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.0171 AC: 2424 AN: 141702 Hom.: 42 Cov.: 31 AF XY: 0.0170 AC XY: 1170 AN XY: 68694

Gnomad4 AFR AF: 0.0415

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00661

Gnomad4 EAS AF: 0.00142

Gnomad4 SAS AF: 0.000447

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.00682

Gnomad4 OTH AF: 0.0132

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs753404083; hg19: chr14-74121531;