chr12-9157290-G-A

Variant names:

• chr12-9157290-G-A
• rs35095552
• NM_002864.3:c.3435C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002864.3(PZP):​c.3435C>T​(p.Thr1145Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00416 in 1,614,060 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0043 (24 hom.)
• Consequence: PZP NM_002864.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0730
• Publications: 3 publications found

Genes affected

PZP (HGNC:9750): (PZP alpha-2-macroglobulin like) The protein encoded by this gene is highly expressed in late-pregnancy serum and is similar in structure to alpha-2-macroglobulin. The encoded protein, which acts as a homotetramer, inhibits the activity of all four classes of proteinases. This protein contains cleavage sites for several proteinases. Upon binding of a proteinase, the conformation of this protein changes to trap the proteinase, limiting its activity. This protein appears to be elevated in the sera of presymptomatic Alzheimer's disease patients. [provided by RefSeq, Dec 2016]

KLRG1 (HGNC:6380): (killer cell lectin like receptor G1) Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. The protein encoded by this gene belongs to the killer cell lectin-like receptor (KLR) family, which is a group of transmembrane proteins preferentially expressed in NK cells. Studies in mice suggested that the expression of this gene may be regulated by MHC class I molecules. [provided by RefSeq, Jun 2016]

LINC00987 (HGNC:48911): (long intergenic non-protein coding RNA 987)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-9157290-G-A is Benign according to our data. Variant chr12-9157290-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2642692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.073 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002864.3. 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
	PZP	NM_002864.3	MANE Select	c.3435C>T	p.Thr1145Thr	synonymous	Exon 28 of 36	NP_002855.2	P20742-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PZP	ENST00000261336.7	TSL:1 MANE Select	c.3435C>T	p.Thr1145Thr	synonymous	Exon 28 of 36	ENSP00000261336.2	P20742-1
	PZP	ENST00000535230.5	TSL:1	n.*2904C>T		non_coding_transcript_exon	Exon 25 of 33	ENSP00000440811.1	F5GXY0
	PZP	ENST00000535230.5	TSL:1	n.*2904C>T		3_prime_UTR	Exon 25 of 33	ENSP00000440811.1	F5GXY0

Frequencies

GnomAD3 genomes AF: 0.00274 AC: 417 AN: 152176 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000676

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00439

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00257 AC: 645 AN: 250744 AF XY: 0.00268

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000509

Gnomad NFE exome AF: 0.00409

Gnomad OTH exome AF: 0.00311

GnomAD4 exome AF: 0.00431 AC: 6306 AN: 1461766 Hom.: 24 Cov.: 31 AF XY: 0.00421 AC XY: 3058 AN XY: 727194

African (AFR) AF: 0.000568 AC: 19 AN: 33476

American (AMR) AF: 0.00280 AC: 125 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000306 AC: 8 AN: 26136

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

South Asian (SAS) AF: 0.00144 AC: 124 AN: 86244

European-Finnish (FIN) AF: 0.000524 AC: 28 AN: 53406

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5766

European-Non Finnish (NFE) AF: 0.00516 AC: 5740 AN: 1111928

Other (OTH) AF: 0.00422 AC: 255 AN: 60390

GnomAD4 genome AF: 0.00273 AC: 416 AN: 152294 Hom.: 2 Cov.: 32 AF XY: 0.00228 AC XY: 170 AN XY: 74466

African (AFR) AF: 0.000674 AC: 28 AN: 41566

American (AMR) AF: 0.00503 AC: 77 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00440 AC: 299 AN: 68030

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00349 Hom.: 1

Bravo AF: 0.00329

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00436

EpiControl AF: 0.00326

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.49
PhyloP100		-0.073
Mutation Taster		=100/0	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: rs35095552; hg19: chr12-9309886;