Variant 14-73654832-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_031427.4(DNAL1):c.4-15T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,507,920 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 5 hom. )

Consequence

DNAL1
NM_031427.4 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.877

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 14-73654832-T-C is Benign according to our data. Variant chr14-73654832-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 195386.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
DNAL1	NM_031427.4 linkuse as main transcript	c.4-15T>C	intron_variant	ENST00000553645.7	NP_113615.2	Q4LDG9-1
DNAL1	NM_001201366.2 linkuse as main transcript	c.-114-15T>C	intron_variant		NP_001188295.1	Q4LDG9-3
DNAL1	XM_017021679.3 linkuse as main transcript	c.-114-15T>C	intron_variant		XP_016877168.1	Q4LDG9-3
DNAL1	XM_024449715.2 linkuse as main transcript	c.-114-15T>C	intron_variant		XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7 linkuse as main transcript	c.4-15T>C		intron_variant		1	NM_031427.4	ENSP00000452037.1		Q4LDG9-1

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

309

AN:

151704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00197

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00365

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00271

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00211

AC:

247

AN:

117202

Hom.:

AF XY:

0.00210

AC XY:

131

AN XY:

62488

show subpopulations

Gnomad AFR exome

AF:

0.000441

Gnomad AMR exome

AF:

0.00218

Gnomad ASJ exome

AF:

0.000726

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00135

Gnomad FIN exome

AF:

0.00332

Gnomad NFE exome

AF:

0.00276

Gnomad OTH exome

AF:

0.00251

GnomAD4 exome

AF:

0.00227

AC:

3076

AN:

1356098

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

1483

AN XY:

668586

show subpopulations

Gnomad4 AFR exome

AF:

0.000310

Gnomad4 AMR exome

AF:

0.00208

Gnomad4 ASJ exome

AF:

0.00100

Gnomad4 EAS exome

AF:

0.0000283

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.00403

Gnomad4 NFE exome

AF:

0.00244

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00204

AC:

309

AN:

151822

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.000386

Gnomad4 AMR

AF:

0.00197

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00365

Gnomad4 NFE

AF:

0.00271

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00270

Hom.:

Bravo

AF:

0.00176

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jul 22, 2014

- -

Primary ciliary dyskinesia 16

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.36

DANN

Benign

0.50

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over