14-73645050-C-A

Variant names:

• chr14-73645050-C-A
• rs1456527977
• NM_031427.4:c.3+8C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031427.4(DNAL1):​c.3+8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: DNAL1 NM_031427.4 splice_region, intron
• Scores: Splicing: ADA: 0.002133
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.3+8C>A		splice_region_variant, intron_variant	Intron 1 of 7	ENST00000553645.7	NP_113615.2
DNAL1	XM_024449715.2	c.-210C>A		5_prime_UTR_variant	Exon 1 of 9		XP_024305483.1
DNAL1	NM_001201366.2	c.-161+8C>A		splice_region_variant, intron_variant	Intron 1 of 8		NP_001188295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.3+8C>A		splice_region_variant, intron_variant	Intron 1 of 7	1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0021
dbscSNV1_RF	Benign	0.13
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: rs1456527977; hg19: chr14-74111753;