Variant 10-101062679-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_030929.5(KAZALD1):c.87C>T(p.Gly29Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,544,824 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 39 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 52 hom. )

Consequence

KAZALD1
NM_030929.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.517

Variant links:

Genes affected

KAZALD1 (HGNC:25460): (Kazal type serine peptidase inhibitor domain 1) This gene encodes a secreted member of the insulin growth factor-binding protein (IGFBP) superfamily. The protein contains an insulin growth factor-binding domain in its N-terminal region, a Kazal-type serine protease inhibitor and follistatin-like domain in its central region, and an immunoglobulin-like domain in its C-terminal region. Studies of the mouse ortholog suggest that this protein may function in bone development and bone regeneration. This gene is hypomethylated and over-expressed in high-grade glioma compared to low-grade glioma, and thus the hypomethylated gene may be associated with cell proliferation and the shorter survival of patients with high-grade glioma. It is also one of numerous genes found to be deleted in a novel 5.54 Mb interstitial deletion, which is associated with multiple congenital anomalies. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

KAZALD1 links:

KAZALD1 (HGNC:):

KAZALD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 10-101062679-C-T is Benign according to our data. Variant chr10-101062679-C-T is described in ClinVar as [Benign]. Clinvar id is 781215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.517 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2105/152358) while in subpopulation AFR AF= 0.0474 (1973/41592). AF 95% confidence interval is 0.0457. There are 39 homozygotes in gnomad4. There are 988 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 39 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KAZALD1	NM_030929.5 linkuse as main transcript	c.87C>T	p.Gly29Gly	synonymous_variant	2/5	ENST00000370200.6	NP_112191.2	Q96I82-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KAZALD1	ENST00000370200.6 linkuse as main transcript	c.87C>T	p.Gly29Gly	synonymous_variant	2/5	1	NM_030929.5	ENSP00000359219.6	Q96I82-1
KAZALD1	ENST00000470106.1 linkuse as main transcript	n.44-307C>T		intron_variant		3
KAZALD1	ENST00000477979.5 linkuse as main transcript	n.112+564C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2098

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0474

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00543

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00337

AC:

484

AN:

143712

Hom.:

AF XY:

0.00227

AC XY:

181

AN XY:

79814

show subpopulations

Gnomad AFR exome

AF:

0.0561

Gnomad AMR exome

AF:

0.00347

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000827

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000275

Gnomad OTH exome

AF:

0.00142

GnomAD4 exome

AF:

0.00152

AC:

2112

AN:

1392466

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

921

AN XY:

689014

show subpopulations

Gnomad4 AFR exome

AF:

0.0464

Gnomad4 AMR exome

AF:

0.00387

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000123

Gnomad4 FIN exome

AF:

0.0000866

Gnomad4 NFE exome

AF:

0.000251

Gnomad4 OTH exome

AF:

0.00305

GnomAD4 genome

AF:

0.0138

AC:

2105

AN:

152358

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

988

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0474

Gnomad4 AMR

AF:

0.00542

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00623

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 16, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.92

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