14-73654765-A-AATAC

Position:

• chr14-73654765-A-AATAC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_031427.4(DNAL1):​c.4-59_4-56dupACAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 1,287,426 control chromosomes in the GnomAD database, including 232 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (161 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (71 hom.)
• Consequence: DNAL1 NM_031427.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.241

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 14-73654765-A-AATAC is Benign according to our data. Variant chr14-73654765-A-AATAC is described in ClinVar as [Benign]. Clinvar id is 1264143.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.4-59_4-56dupACAT		intron_variant		ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.-114-59_-114-56dupACAT		intron_variant			NP_001188295.1
DNAL1	XM_017021679.3	c.-114-59_-114-56dupACAT		intron_variant			XP_016877168.1
DNAL1	XM_024449715.2	c.-114-59_-114-56dupACAT		intron_variant			XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.4-82_4-81insATAC		intron_variant		1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4217 AN: 151644 Hom.: 157 Cov.: 31

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000953

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000692

Gnomad OTH AF: 0.0207

GnomAD4 exome AF: 0.00238 AC: 2700 AN: 1135676 Hom.: 71 AF XY: 0.00224 AC XY: 1260 AN XY: 561770

Gnomad4 AFR exome AF: 0.0672

Gnomad4 AMR exome AF: 0.00628

Gnomad4 ASJ exome AF: 0.0162

Gnomad4 EAS exome AF: 0.00105

Gnomad4 SAS exome AF: 0.000471

Gnomad4 FIN exome AF: 0.0000320

Gnomad4 NFE exome AF: 0.000374

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.0279 AC: 4241 AN: 151750 Hom.: 161 Cov.: 31 AF XY: 0.0266 AC XY: 1974 AN XY: 74164

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000953

Gnomad4 NFE AF: 0.000692

Gnomad4 OTH AF: 0.0205

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 24, 2021

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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;