rs201032080

Variant summary

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

The NM_144688.5(KASH5):​c.38C>G​(p.Ala13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000963 in 1,453,408 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A13V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000096 ( 1 hom. )

Consequence

KASH5
NM_144688.5 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.333
Variant links:
Genes affected
KASH5 (HGNC:26520): (KASH domain containing 5) Predicted to enable dynein complex binding activity. Predicted to be involved in several processes, including cytoskeleton organization; homologous chromosome segregation; and spindle localization. Predicted to act upstream of or within double-strand break repair via homologous recombination; oogenesis; and spermatogenesis. Predicted to be integral component of membrane. Predicted to be part of meiotic nuclear membrane microtubule tethering complex. Predicted to be active in chromosome; meiotic spindle pole; and nuclear outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.12651724).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KASH5NM_144688.5 linkc.38C>G p.Ala13Gly missense_variant Exon 2 of 20 ENST00000447857.8 NP_653289.3 Q8N6L0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KASH5ENST00000447857.8 linkc.38C>G p.Ala13Gly missense_variant Exon 2 of 20 1 NM_144688.5 ENSP00000404220.2 Q8N6L0

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000422
AC:
1
AN:
236844
Hom.:
0
AF XY:
0.00000772
AC XY:
1
AN XY:
129460
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.00000940
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000963
AC:
14
AN:
1453408
Hom.:
1
Cov.:
36
AF XY:
0.0000138
AC XY:
10
AN XY:
723068
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000828
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.028
T;T
Eigen
Benign
-0.086
Eigen_PC
Benign
-0.30
FATHMM_MKL
Benign
0.086
N
LIST_S2
Benign
0.57
T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.4
N;.
REVEL
Benign
0.10
Sift
Benign
0.042
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.25
MutPred
0.042
Loss of glycosylation at T12 (P = 0.1591);Loss of glycosylation at T12 (P = 0.1591);
MVP
0.53
MPC
0.49
ClinPred
0.32
T
GERP RS
3.4
Varity_R
0.075
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs201032080; hg19: chr19-49894178; API