rs576147534

Positions:

• chr14-73654843-A-G
• chr14-73654843-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031427.4(DNAL1):​c.4-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,205,102 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: DNAL1 NM_031427.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002819
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.4-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.-114-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001188295.1
DNAL1	XM_017021679.3	c.-114-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_016877168.1
DNAL1	XM_024449715.2	c.-114-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.4-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_031427.4	ENSP00000452037	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000249 AC: 3 AN: 1205102 Hom.: 0 Cov.: 33 AF XY: 0.00000507 AC XY: 3 AN XY: 591486

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000518

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.8
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		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: rs576147534; hg19: chr14-74121546;