14-73655011-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031427.4(DNAL1):c.42+126T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 924,828 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (36 hom.)
• Consequence: DNAL1 NM_031427.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.745

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-73655011-T-C is Benign according to our data. Variant chr14-73655011-T-C is described in ClinVar as [Benign]. Clinvar id is 1259153.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAL1	NM_031427.4	c.42+126T>C		intron_variant		ENST00000553645.7
DNAL1	NM_001201366.2	c.-76+126T>C		intron_variant
DNAL1	XM_017021679.3	c.-76+126T>C		intron_variant
DNAL1	XM_024449715.2	c.-76+126T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAL1	ENST00000553645.7	c.42+126T>C		intron_variant		1	NM_031427.4	P1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2503 AN: 152128 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00629

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00235 AC: 1816 AN: 772582 Hom.: 36 AF XY: 0.00209 AC XY: 828 AN XY: 396750

Gnomad4 AFR exome AF: 0.0527

Gnomad4 AMR exome AF: 0.00464

Gnomad4 ASJ exome AF: 0.0202

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000249

Gnomad4 FIN exome AF: 0.0000275

Gnomad4 NFE exome AF: 0.000290

Gnomad4 OTH exome AF: 0.00705

GnomAD4 genome AF: 0.0165 AC: 2517 AN: 152246 Hom.: 56 Cov.: 32 AF XY: 0.0160 AC XY: 1191 AN XY: 74458

Gnomad4 AFR AF: 0.0550

Gnomad4 AMR AF: 0.00628

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0132 Hom.: 6

Bravo AF: 0.0190

Asia WGS AF: 0.00260 AC: 10 AN: 3476

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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	9.6
Dann	Benign	0.72

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: rs73295381; hg19: chr14-74121714;