chr1-37565095-T-C

Position:

• chr1-37565095-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003462.5(DNALI1):​c.*34T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,608,438 control chromosomes in the GnomAD database, including 163,425 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (13466 hom., cov: 32)
  • Exomes 𝑓: 0.45 (149959 hom.)
• Consequence: DNALI1 NM_003462.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671

Genes affected

DNALI1 (HGNC:14353): (dynein axonemal light intermediate chain 1) This gene is the human homolog of the Chlamydomonas inner dynein arm gene, p28. The precise function of this gene is not known, however, it is a potential candidate for immotile cilia syndrome (ICS). Ultrastructural defects of the inner dynein arms are seen in patients with ICS. Immotile mutant strains of Chlamydomonas, a biflagellated algae, exhibit similar defects. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNALI1	NM_003462.5	c.*34T>C		3_prime_UTR_variant	6/6	ENST00000652629.1	NP_003453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNALI1	ENST00000652629.1	c.*34T>C		3_prime_UTR_variant	6/6		NM_003462.5	ENSP00000498620	P1
DNALI1	ENST00000296218.8	c.*34T>C		3_prime_UTR_variant	6/6	1		ENSP00000296218
DNALI1	ENST00000467277.1	n.570T>C		non_coding_transcript_exon_variant	3/3	2
DNALI1	ENST00000497858.1	n.1778T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61669 AN: 151952 Hom.: 13444 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.428

GnomAD3 exomes AF: 0.456 AC: 114505 AN: 251240 Hom.: 27751 AF XY: 0.446 AC XY: 60588 AN XY: 135792

Gnomad AFR exome AF: 0.240

Gnomad AMR exome AF: 0.608

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.566

Gnomad SAS exome AF: 0.322

Gnomad FIN exome AF: 0.550

Gnomad NFE exome AF: 0.451

Gnomad OTH exome AF: 0.445

GnomAD4 exome AF: 0.448 AC: 652320 AN: 1456368 Hom.: 149959 Cov.: 31 AF XY: 0.443 AC XY: 321052 AN XY: 724748

Gnomad4 AFR exome AF: 0.237

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.595

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.547

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.406 AC: 61726 AN: 152070 Hom.: 13466 Cov.: 32 AF XY: 0.409 AC XY: 30406 AN XY: 74326

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.351

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.431

Alfa AF: 0.435 Hom.: 26241

Bravo AF: 0.401

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.7
DANN	Benign	0.81

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: rs6619; hg19: chr1-38030696; COSMIC: COSV56169328; COSMIC: COSV56169328;