Variant chr1-37557737-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003462.5(DNALI1):c.216A>G(p.Ile72Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,613,726 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I72V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00090 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

DNALI1
NM_003462.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0810

Variant links:

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 links:

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ACMG classification

Classification made for transcript

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 (MetaRNN=0.09365544).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNALI1	NM_003462.5 link	c.216A>G	p.Ile72Met	missense_variant	2/6	ENST00000652629.1	NP_003453.3	O14645-1A0A499FIY3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNALI1	ENST00000652629.1 link	c.216A>G	p.Ile72Met	missense_variant	2/6		NM_003462.5	ENSP00000498620.1	O14645-1
DNALI1	ENST00000296218.8 link	c.282A>G	p.Ile94Met	missense_variant	2/6	1		ENSP00000296218.7	A0A499FIY3
DNALI1	ENST00000466723.1 link	n.213A>G		non_coding_transcript_exon_variant	2/4	2
DNALI1	ENST00000490312.1 link	n.258A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000900

AC:

137

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000652

AC:

163

AN:

250178

Hom.:

AF XY:

0.000606

AC XY:

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.0000999

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00124

AC:

1807

AN:

1461418

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

872

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00153

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.000899

AC:

137

AN:

152308

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00153

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00139

Hom.:

Bravo

AF:

0.000918

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000782

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00154

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 26, 2023

The c.282A>G (p.I94M) alteration is located in exon 2 (coding exon 2) of the DNALI1 gene. This alteration results from a A to G substitution at nucleotide position 282, causing the isoleucine (I) at amino acid position 94 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.55

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.73

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.038

MetaRNN

Benign

0.094

MetaSVM

Benign

-0.85

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.42

Sift

Uncertain

0.028

Sift4G

Uncertain

0.054

Vest4

0.75

MVP

0.16

MPC

0.21

ClinPred

0.078

GERP RS

0.18

gMVP

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over