10-101065003-G-T

Variant names:

• chr10-101065003-G-T
• rs12359843
• NM_030929.5:c.*83G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030929.5(KAZALD1):​c.*83G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 998,274 control chromosomes in the GnomAD database, including 7,997 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.096 (1002 hom., cov: 33)
  • Exomes 𝑓: 0.12 (6995 hom.)
• Consequence: KAZALD1 NM_030929.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAZALD1	NM_030929.5	c.*83G>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000370200.6	NP_112191.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAZALD1	ENST00000370200.6	c.*83G>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_030929.5	ENSP00000359219.6
KAZALD1	ENST00000477979.5	n.654G>T		non_coding_transcript_exon_variant	Exon 4 of 4	3
KAZALD1	ENST00000477267.1	n.453+60G>T		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.0959 AC: 14583 AN: 152130 Hom.: 1000 Cov.: 33

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0932

GnomAD4 exome AF: 0.119 AC: 100436 AN: 846026 Hom.: 6995 Cov.: 11 AF XY: 0.121 AC XY: 53405 AN XY: 439908

African (AFR) AF: 0.0199 AC: 425 AN: 21356

American (AMR) AF: 0.115 AC: 4150 AN: 36110

Ashkenazi Jewish (ASJ) AF: 0.0945 AC: 1972 AN: 20872

East Asian (EAS) AF: 0.00130 AC: 46 AN: 35370

South Asian (SAS) AF: 0.175 AC: 12142 AN: 69550

European-Finnish (FIN) AF: 0.214 AC: 10535 AN: 49294

Middle Eastern (MID) AF: 0.0637 AC: 224 AN: 3514

European-Non Finnish (NFE) AF: 0.117 AC: 66687 AN: 570046

Other (OTH) AF: 0.107 AC: 4255 AN: 39914

GnomAD4 genome AF: 0.0958 AC: 14592 AN: 152248 Hom.: 1002 Cov.: 33 AF XY: 0.0999 AC XY: 7436 AN XY: 74434

African (AFR) AF: 0.0219 AC: 910 AN: 41542

American (AMR) AF: 0.0972 AC: 1488 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 352 AN: 3470

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5186

South Asian (SAS) AF: 0.185 AC: 893 AN: 4826

European-Finnish (FIN) AF: 0.214 AC: 2269 AN: 10596

Middle Eastern (MID) AF: 0.0548 AC: 16 AN: 292

European-Non Finnish (NFE) AF: 0.123 AC: 8357 AN: 68008

Other (OTH) AF: 0.0960 AC: 203 AN: 2114

Alfa AF: 0.102 Hom.: 1186

Bravo AF: 0.0817

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.42
DANN	Benign	0.48
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12359843; hg19: chr10-102824760; COSMIC: COSV64630078; COSMIC: COSV64630078;