chr1-37565095-T-C

Variant names:

• chr1-37565095-T-C
• rs6619
• NM_003462.5:c.*34T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 32 publications found

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]

DNALI1 Gene-Disease associations (from GenCC):

• spermatogenic failure 83

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNALI1	NM_003462.5	c.*34T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000652629.1	NP_003453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNALI1	ENST00000652629.1	c.*34T>C		3_prime_UTR_variant	Exon 6 of 6		NM_003462.5	ENSP00000498620.1
DNALI1	ENST00000296218.8	c.*34T>C		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000296218.7
DNALI1	ENST00000467277.1	n.570T>C		non_coding_transcript_exon_variant	Exon 3 of 3	2
DNALI1	ENST00000497858.1	n.1778T>C		non_coding_transcript_exon_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.456 AC: 114505 AN: 251240 AF XY: 0.446

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 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

African (AFR) AF: 0.237 AC: 7909 AN: 33406

American (AMR) AF: 0.599 AC: 26779 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9382 AN: 26108

East Asian (EAS) AF: 0.595 AC: 23609 AN: 39672

South Asian (SAS) AF: 0.320 AC: 27612 AN: 86174

European-Finnish (FIN) AF: 0.547 AC: 29212 AN: 53360

Middle Eastern (MID) AF: 0.311 AC: 1788 AN: 5744

European-Non Finnish (NFE) AF: 0.452 AC: 499889 AN: 1107004

Other (OTH) AF: 0.434 AC: 26140 AN: 60194

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

African (AFR) AF: 0.245 AC: 10160 AN: 41490

American (AMR) AF: 0.512 AC: 7823 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3468

East Asian (EAS) AF: 0.583 AC: 3012 AN: 5170

South Asian (SAS) AF: 0.319 AC: 1539 AN: 4828

European-Finnish (FIN) AF: 0.536 AC: 5653 AN: 10552

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30912 AN: 67954

Other (OTH) AF: 0.431 AC: 913 AN: 2116

Alfa AF: 0.427 Hom.: 40369

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
PhyloP100		0.67
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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