Variant 19-49398101-G-T 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_144688.5(KASH5):c.587G>T(p.Arg196Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KASH5
NM_144688.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35

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]

KASH5 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=0.12811592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KASH5	NM_144688.5 linkuse as main transcript	c.587G>T	p.Arg196Leu	missense_variant	7/20	ENST00000447857.8	NP_653289.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KASH5	ENST00000447857.8 linkuse as main transcript	c.587G>T	p.Arg196Leu	missense_variant	7/20	1	NM_144688.5	ENSP00000404220	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453422

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721224

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Nov 20, 2023

The c.587G>T (p.R196L) alteration is located in exon 7 (coding exon 6) of the CCDC155 gene. This alteration results from a G to T substitution at nucleotide position 587, causing the arginine (R) at amino acid position 196 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.6

D;.

REVEL

Benign

0.095

Sift

Uncertain

0.022

D;.

Sift4G

Uncertain

0.0080

D;.

Polyphen

0.16

B;.

Vest4

0.48

MutPred

0.21

Loss of MoRF binding (P = 0.0628);.;

MVP

0.37

MPC

0.31

ClinPred

0.72

GERP RS

1.8

Varity_R

0.20

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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