NM_030929.5:c.511+564G>C

Variant names:

• chr10-101063667-G-C
• rs807038
• NM_030929.5:c.511+564G>C

Variant summary

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

The NM_030929.5(KAZALD1):​c.511+564G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.807 in 152,220 control chromosomes in the GnomAD database, including 49,821 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 0.81 (49821 hom., cov: 33)
• Consequence: KAZALD1 NM_030929.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030929.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZALD1	NM_030929.5	MANE Select	c.511+564G>C		intron	N/A	NP_112191.2
	KAZALD1	NM_001319303.2		c.43-539G>C		intron	N/A	NP_001306232.1
	KAZALD1	NR_135067.2		n.128-594G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZALD1	ENST00000370200.6	TSL:1 MANE Select	c.511+564G>C		intron	N/A	ENSP00000359219.6
	KAZALD1	ENST00000470106.1	TSL:3	n.162-539G>C		intron	N/A
	KAZALD1	ENST00000477267.1	TSL:5	n.26+564G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.807 AC: 122747 AN: 152102 Hom.: 49780 Cov.: 33

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.804

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.807 AC: 122838 AN: 152220 Hom.: 49821 Cov.: 33 AF XY: 0.799 AC XY: 59466 AN XY: 74422

African (AFR) AF: 0.860 AC: 35726 AN: 41526

American (AMR) AF: 0.761 AC: 11647 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2845 AN: 3472

East Asian (EAS) AF: 0.605 AC: 3121 AN: 5162

South Asian (SAS) AF: 0.686 AC: 3309 AN: 4822

European-Finnish (FIN) AF: 0.757 AC: 8027 AN: 10604

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.816 AC: 55480 AN: 68018

Other (OTH) AF: 0.805 AC: 1700 AN: 2112

Alfa AF: 0.774 Hom.: 2711

Bravo AF: 0.810

Asia WGS AF: 0.691 AC: 2401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.74
PhyloP100		-0.23
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: rs807038; hg19: chr10-102823424;