chr1-37561685-A-G

Variant summary

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

The NM_003462.5(DNALI1):ā€‹c.526A>Gā€‹(p.Met176Val) variant causes a missense change. The variant allele was found at a frequency of 0.000201 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00022 ( 0 hom., cov: 32)
Exomes š‘“: 0.00020 ( 0 hom. )

Consequence

DNALI1
NM_003462.5 missense

Scores

4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37
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]

Genome browser will be placed here

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=0.2265484).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNALI1NM_003462.5 linkuse as main transcriptc.526A>G p.Met176Val missense_variant 4/6 ENST00000652629.1 NP_003453.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNALI1ENST00000652629.1 linkuse as main transcriptc.526A>G p.Met176Val missense_variant 4/6 NM_003462.5 ENSP00000498620 P1O14645-1

Frequencies

GnomAD3 genomes
AF:
0.000217
AC:
33
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000456
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000151
AC:
38
AN:
251056
Hom.:
0
AF XY:
0.000147
AC XY:
20
AN XY:
135726
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000255
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000199
AC:
291
AN:
1461872
Hom.:
0
Cov.:
31
AF XY:
0.000208
AC XY:
151
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000239
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.000217
AC:
33
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.000202
AC XY:
15
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000456
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000325
Hom.:
0
Bravo
AF:
0.000185
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000123
AC:
15
EpiCase
AF:
0.000872
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsJun 22, 2021The c.592A>G (p.M198V) alteration is located in exon 4 (coding exon 4) of the DNALI1 gene. This alteration results from a A to G substitution at nucleotide position 592, causing the methionine (M) at amino acid position 198 to be replaced by a valine (V). 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
0.35
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Uncertain
0.98
Eigen
Benign
0.048
Eigen_PC
Benign
0.20
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.82
T
M_CAP
Benign
0.0067
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-2.1
N
REVEL
Benign
0.078
Sift
Benign
0.15
T
Sift4G
Benign
0.24
T
Vest4
0.39
MVP
0.23
MPC
0.11
ClinPred
0.040
T
GERP RS
5.2
gMVP
0.56

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.

Other links and lift over

dbSNP: rs200794930; hg19: chr1-38027286; API