14-73655058-T-G

Position:

• chr14-73655058-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031427.4(DNAL1):​c.42+173T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 151,756 control chromosomes in the GnomAD database, including 2,169 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.12 (2169 hom., cov: 31)
• Consequence: DNAL1 NM_031427.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.04

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 14-73655058-T-G is Benign according to our data. Variant chr14-73655058-T-G is described in ClinVar as [Benign]. Clinvar id is 1181919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.42+173T>G		intron_variant		ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.-76+173T>G		intron_variant			NP_001188295.1
DNAL1	XM_017021679.3	c.-76+173T>G		intron_variant			XP_016877168.1
DNAL1	XM_024449715.2	c.-76+173T>G		intron_variant			XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.42+173T>G		intron_variant		1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18212 AN: 151638 Hom.: 2173 Cov.: 31

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.0957

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.137

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 18209 AN: 151756 Hom.: 2169 Cov.: 31 AF XY: 0.130 AC XY: 9648 AN XY: 74158

Gnomad4 AFR AF: 0.0275

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.0957

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0641 Hom.: 82

Bravo AF: 0.124

Asia WGS AF: 0.360 AC: 1249 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.64

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: rs11622678; hg19: chr14-74121761;