rs807037

Variant names:

• chr10-101064592-G-A
• rs807037
• NM_030929.5:c.764G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-101064592-G-A
• chr10-101064592-G-C
• chr10-101064592-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030929.5(KAZALD1):​c.764G>A​(p.Gly255Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: KAZALD1 NM_030929.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.18
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4115916).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZALD1	NM_030929.5	MANE Select	c.764G>A	p.Gly255Asp	missense	Exon 4 of 5	NP_112191.2
	KAZALD1	NM_001319303.2		c.350G>A	p.Gly117Asp	missense	Exon 4 of 6	NP_001306232.1
	KAZALD1	NR_135067.2		n.380G>A		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAZALD1	ENST00000370200.6	TSL:1 MANE Select	c.764G>A	p.Gly255Asp	missense	Exon 4 of 5	ENSP00000359219.6	Q96I82-1
	KAZALD1	ENST00000891380.1		c.764G>A	p.Gly255Asp	missense	Exon 4 of 6	ENSP00000561439.1
	KAZALD1	ENST00000952668.1		c.764G>A	p.Gly255Asp	missense	Exon 3 of 4	ENSP00000622727.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461624 Hom.: 0 Cov.: 67 AF XY: 0.00000550 AC XY: 4 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	0.0066	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	-0.056
Eigen_PC	Benign	0.098
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.2
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.050	B
Vest4		0.52
MutPred		0.71		Gain of phosphorylation at Y251 (P = 0.1219)
MVP		0.73
MPC		0.45
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.82
gMVP		0.94
Mutation Taster		=85/15	polymorphism

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: rs807037; hg19: chr10-102824349;