Variant 14-73661975-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_031427.4(DNAL1):c.153-12G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000736 in 1,533,590 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 4 hom. )

Consequence

DNAL1
NM_031427.4 intron

Scores

Splicing: ADA: 0.00004958

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.16

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 14-73661975-G-C is Benign according to our data. Variant chr14-73661975-G-C is described in ClinVar as [Benign]. Clinvar id is 261957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-73661975-G-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
DNAL1	NM_031427.4 linkuse as main transcript	c.153-12G>C	intron_variant	ENST00000553645.7	NP_113615.2	Q4LDG9-1
DNAL1	NM_001201366.2 linkuse as main transcript	c.36-12G>C	intron_variant		NP_001188295.1	Q4LDG9-3
DNAL1	XM_017021679.3 linkuse as main transcript	c.36-12G>C	intron_variant		XP_016877168.1	Q4LDG9-3
DNAL1	XM_024449715.2 linkuse as main transcript	c.36-12G>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.153-12G>C		intron_variant		1	NM_031427.4	ENSP00000452037.1		Q4LDG9-1

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

593

AN:

151894

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

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:

0.0000442

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00109

AC:

164

AN:

150196

Hom.:

AF XY:

0.000835

AC XY:

AN XY:

79018

show subpopulations

Gnomad AFR exome

AF:

0.0168

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000709

GnomAD4 exome

AF:

0.000388

AC:

536

AN:

1381578

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

221

AN XY:

680884

show subpopulations

Gnomad4 AFR exome

AF:

0.0138

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000268

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000140

Gnomad4 OTH exome

AF:

0.000820

GnomAD4 genome

AF:

0.00390

AC:

593

AN:

152012

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

273

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00278

Hom.:

Bravo

AF:

0.00478

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 16

Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 21, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 14, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000050

dbscSNV1_RF

Benign

0.0040

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