2-218634220-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_032726.4(PLCD4):c.1722G>A(p.Met574Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,607,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

PLCD4
NM_032726.4 missense, splice_region

Scores

Splicing: ADA: 0.003204

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.196

Publications

3 publications found

Variant links:

Genes affected

PLCD4 (HGNC:9062): (phospholipase C delta 4) This gene encodes a member of the delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer. [provided by RefSeq, Jan 2011]

PLCD4 links:

ZNF142 (HGNC:12927): (zinc finger protein 142) The protein encoded by this gene belongs to the Kruppel family of C2H2-type zinc finger proteins. It contains 31 C2H2-type zinc fingers and may be involved in transcriptional regulation. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2013]

ZNF142 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with impaired speech and hyperkinetic movements
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ZNF142 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19701833).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032726.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLCD4	NM_032726.4	MANE Select	c.1722G>A	p.Met574Ile	missense splice_region	Exon 12 of 16	NP_116115.1	Q9BRC7-1
ZNF142	NM_001379659.1	MANE Select	c.*4119C>T		3_prime_UTR	Exon 11 of 11	NP_001366588.1	A0A7P0N7C4
ZNF142	NM_001366290.3		c.*4119C>T		3_prime_UTR	Exon 10 of 10	NP_001353219.1	A0A7P0N7C4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PLCD4	ENST00000450993.7	TSL:1 MANE Select	c.1722G>A	p.Met574Ile	missense splice_region	Exon 12 of 16	ENSP00000388631.2	Q9BRC7-1
PLCD4	ENST00000432688.5	TSL:5	c.1818G>A	p.Met606Ile	missense splice_region	Exon 13 of 17	ENSP00000396185.1	C9JEA7
PLCD4	ENST00000417849.5	TSL:5	c.1722G>A	p.Met574Ile	missense splice_region	Exon 12 of 17	ENSP00000396942.1	Q9BRC7-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000122

AC:

AN:

237226

AF XY:

0.000109

show subpopulations

Gnomad AFR exome

AF:

0.000139

Gnomad AMR exome

AF:

0.000274

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000168

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000145

AC:

211

AN:

1455720

Hom.:

Cov.:

AF XY:

0.000124

AC XY:

AN XY:

723480

show subpopulations

African (AFR)

AF:

0.0000899

AC:

AN:

33382

American (AMR)

AF:

0.000207

AC:

AN:

43478

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26000

East Asian (EAS)

AF:

0.00

AC:

AN:

39536

South Asian (SAS)

AF:

0.00

AC:

AN:

85224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000175

AC:

194

AN:

1109040

Other (OTH)

AF:

0.0000831

AC:

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000138

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.000785

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.000162

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000251

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000992

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.17

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.77

M_CAP

Benign

0.0053

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.18

PhyloP100

0.20

PrimateAI

Benign

0.46

PROVEAN

Benign

0.49

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0050

Vest4

0.34

MutPred

0.84

Gain of sheet (P = 0.0827)

MVP

0.75

MPC

0.25

ClinPred

0.017

GERP RS

5.3

Varity_R

0.17

gMVP

0.30

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0032

dbscSNV1_RF

Benign

0.13

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over