chr12-25108698-T-A

Variant summary

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

The NM_018272.5(DNAI7):​c.2019A>T​(p.Lys673Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

DNAI7
NM_018272.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.466
Variant links:
Genes affected
DNAI7 (HGNC:29599): (dynein axonemal intermediate chain 7) Predicted to enable beta-tubulin binding activity and microtubule binding activity. Predicted to be located in cilium; cytoplasm; and microtubule cytoskeleton. Predicted to be part of axonemal dynein complex. Predicted to be active in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.07033408).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAI7NM_018272.5 linkuse as main transcriptc.2019A>T p.Lys673Asn missense_variant 16/16 ENST00000395987.8 NP_060742.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAI7ENST00000395987.8 linkuse as main transcriptc.2019A>T p.Lys673Asn missense_variant 16/161 NM_018272.5 ENSP00000379310 A1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

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 GeneticsFeb 28, 2023The c.2019A>T (p.K673N) alteration is located in exon 16 (coding exon 16) of the CASC1 gene. This alteration results from a A to T substitution at nucleotide position 2019, causing the lysine (K) at amino acid position 673 to be replaced by an asparagine (N). 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
Benign
0.26
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
9.5
DANN
Uncertain
0.98
DEOGEN2
Benign
0.021
T;T;.;.
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.56
FATHMM_MKL
Benign
0.099
N
LIST_S2
Benign
0.83
T;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.070
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.7
.;L;.;.
MutationTaster
Benign
0.81
D;D;N;N;N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.040
Sift
Benign
0.16
T;T;T;T
Sift4G
Benign
0.083
T;T;T;T
Polyphen
0.59
P;P;.;.
Vest4
0.11
MutPred
0.32
Loss of ubiquitination at K673 (P = 0.003);.;.;.;
MVP
0.22
MPC
0.14
ClinPred
0.27
T
GERP RS
1.0
Varity_R
0.067
gMVP
0.22

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: rs920345033; hg19: chr12-25261632; API