Variant 14-73654843-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_031427.4(DNAL1):c.4-4A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,188,308 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAL1
NM_031427.4 splice_region, intron

Scores

Splicing: ADA: 0.00003782

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0200

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 -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 14-73654843-A-T is Benign according to our data. Variant chr14-73654843-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 414000.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00132 (1574/1188308) while in subpopulation AMR AF= 0.00616 (115/18670). AF 95% confidence interval is 0.00525. There are 0 homozygotes in gnomad4_exome. There are 811 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
DNAL1	NM_031427.4 link	c.4-4A>T	splice_region_variant, intron_variant	ENST00000553645.7	NP_113615.2	Q4LDG9-1
DNAL1	NM_001201366.2 link	c.-114-4A>T	splice_region_variant, intron_variant		NP_001188295.1	Q4LDG9-3
DNAL1	XM_017021679.3 link	c.-114-4A>T	splice_region_variant, intron_variant		XP_016877168.1	Q4LDG9-3
DNAL1	XM_024449715.2 link	c.-114-4A>T	splice_region_variant, intron_variant		XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7 link	c.4-4A>T		splice_region_variant, intron_variant		1	NM_031427.4	ENSP00000452037.1		Q4LDG9-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

148814

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00367

AC:

338

AN:

92032

Hom.:

AF XY:

0.00362

AC XY:

180

AN XY:

49670

show subpopulations

Gnomad AFR exome

AF:

0.00300

Gnomad AMR exome

AF:

0.00963

Gnomad ASJ exome

AF:

0.00177

Gnomad EAS exome

AF:

0.00598

Gnomad SAS exome

AF:

0.00313

Gnomad FIN exome

AF:

0.00261

Gnomad NFE exome

AF:

0.00260

Gnomad OTH exome

AF:

0.00429

GnomAD4 exome

AF:

0.00132

AC:

1574

AN:

1188308

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

811

AN XY:

582942

show subpopulations

Gnomad4 AFR exome

AF:

0.00175

Gnomad4 AMR exome

AF:

0.00616

Gnomad4 ASJ exome

AF:

0.00250

Gnomad4 EAS exome

AF:

0.00321

Gnomad4 SAS exome

AF:

0.00362

Gnomad4 FIN exome

AF:

0.00259

Gnomad4 NFE exome

AF:

0.000934

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000201

AC:

AN:

148908

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72566

show subpopulations

Gnomad4 AFR

AF:

0.0000247

Gnomad4 AMR

AF:

0.000133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00436

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 16

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 06, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.45

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000038

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.020

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