NM_031427.4:c.4-6_4-5dupTT

Variant names:

• chr14-73654828-C-CTT
• rs753404083
• NM_031427.4:c.4-6_4-5dupTT

Variant summary

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

The NM_031427.4(DNAL1):​c.4-6_4-5dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,337,106 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000070 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: DNAL1 NM_031427.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAL1	NM_031427.4	c.4-6_4-5dupTT		splice_region_variant, intron_variant	Intron 1 of 7	ENST00000553645.7	NP_113615.2
DNAL1	NM_001201366.2	c.-114-6_-114-5dupTT		splice_region_variant, intron_variant	Intron 2 of 8		NP_001188295.1
DNAL1	XM_017021679.3	c.-114-6_-114-5dupTT		splice_region_variant, intron_variant	Intron 2 of 8		XP_016877168.1
DNAL1	XM_024449715.2	c.-114-6_-114-5dupTT		splice_region_variant, intron_variant	Intron 2 of 8		XP_024305483.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAL1	ENST00000553645.7	c.4-19_4-18insTT		intron_variant	Intron 1 of 7	1	NM_031427.4	ENSP00000452037.1

Frequencies

GnomAD3 genomes AF: 0.00000704 AC: 1 AN: 142138 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000552 AC: 41 AN: 74314 Hom.: 0 AF XY: 0.000446 AC XY: 18 AN XY: 40328

Gnomad AFR exome AF: 0.00115

Gnomad AMR exome AF: 0.000922

Gnomad ASJ exome AF: 0.000214

Gnomad EAS exome AF: 0.000189

Gnomad SAS exome AF: 0.000465

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.000479

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.000172 AC: 205 AN: 1194968 Hom.: 0 Cov.: 0 AF XY: 0.000194 AC XY: 115 AN XY: 591692

Gnomad4 AFR exome AF: 0.000194

Gnomad4 AMR exome AF: 0.000524

Gnomad4 ASJ exome AF: 0.000187

Gnomad4 EAS exome AF: 0.000189

Gnomad4 SAS exome AF: 0.000555

Gnomad4 FIN exome AF: 0.000280

Gnomad4 NFE exome AF: 0.000131

Gnomad4 OTH exome AF: 0.000161

GnomAD4 genome AF: 0.00000704 AC: 1 AN: 142138 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 68926

Gnomad4 AFR AF: 0.0000257

Gnomad4 AMR AF: 0.00

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs753404083; hg19: chr14-74121531;