1-37556953-A-T

Variant names:

• chr1-37556953-A-T
• rs780088232
• ENST00000296218.8:c.25A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000296218.8(DNALI1):​c.25A>T​(p.Thr9Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNALI1 ENST00000296218.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.88
• Publications: 2 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0714941).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000296218.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNALI1	NM_003462.5	MANE Select	c.-42A>T		5_prime_UTR	Exon 1 of 6	NP_003453.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNALI1	ENST00000296218.8	TSL:1	c.25A>T	p.Thr9Ser	missense	Exon 1 of 6	ENSP00000296218.7	A0A499FIY3
	DNALI1	ENST00000652629.1	MANE Select	c.-42A>T		5_prime_UTR	Exon 1 of 6	ENSP00000498620.1	O14645-1
	DNALI1	ENST00000970663.1		c.-42A>T		5_prime_UTR	Exon 1 of 6	ENSP00000640722.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.22
DANN	Benign	0.67
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.99	T
PhyloP100		-1.9
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.0070
Sift	Benign	0.055	T
Sift4G	Benign	0.75	T
Vest4		0.15
MutPred		0.21		Gain of glycosylation at T9 (P = 0.0115)
MVP		0.048
MPC		0.078
ClinPred		0.43	T
GERP RS		-8.2
PromoterAI		-0.17	Neutral
gMVP		0.25
Mutation Taster		=97/3	polymorphism

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: rs780088232; hg19: chr1-38022554;