NM_032726.4:c.1659C>T

Variant names:

• chr2-218634157-C-T
• rs183605922
• NM_032726.4:c.1659C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_032726.4(PLCD4):​c.1659C>T​(p.Ser553Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,612,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00080 (0 hom.)
• Consequence: PLCD4 NM_032726.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.908
• Publications: 0 publications found

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]

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)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 2-218634157-C-T is Benign according to our data. Variant chr2-218634157-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3388287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.908 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCD4	NM_032726.4	MANE Select	c.1659C>T	p.Ser553Ser	synonymous	Exon 12 of 16	NP_116115.1	Q9BRC7-1
	ZNF142	NM_001379659.1	MANE Select	c.*4182G>A		3_prime_UTR	Exon 11 of 11	NP_001366588.1	A0A7P0N7C4
	ZNF142	NM_001366290.3		c.*4182G>A		3_prime_UTR	Exon 10 of 10	NP_001353219.1	A0A7P0N7C4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCD4	ENST00000450993.7	TSL:1 MANE Select	c.1659C>T	p.Ser553Ser	synonymous	Exon 12 of 16	ENSP00000388631.2	Q9BRC7-1
	PLCD4	ENST00000432688.5	TSL:5	c.1755C>T	p.Ser585Ser	synonymous	Exon 13 of 17	ENSP00000396185.1	C9JEA7
	PLCD4	ENST00000417849.5	TSL:5	c.1659C>T	p.Ser553Ser	synonymous	Exon 12 of 17	ENSP00000396942.1	Q9BRC7-1

Frequencies

GnomAD3 genomes AF: 0.000591 AC: 90 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000999

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000584 AC: 144 AN: 246610 AF XY: 0.000531

Gnomad AFR exome AF: 0.0000657

Gnomad AMR exome AF: 0.0000586

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00154

Gnomad NFE exome AF: 0.000868

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.000798 AC: 1166 AN: 1460378 Hom.: 0 Cov.: 32 AF XY: 0.000771 AC XY: 560 AN XY: 726364

African (AFR) AF: 0.0000598 AC: 2 AN: 33456

American (AMR) AF: 0.000112 AC: 5 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26104

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85888

European-Finnish (FIN) AF: 0.00131 AC: 70 AN: 53338

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.000931 AC: 1035 AN: 1111338

Other (OTH) AF: 0.000663 AC: 40 AN: 60338

GnomAD4 genome AF: 0.000591 AC: 90 AN: 152294 Hom.: 0 Cov.: 33 AF XY: 0.000671 AC XY: 50 AN XY: 74468

African (AFR) AF: 0.000192 AC: 8 AN: 41560

American (AMR) AF: 0.000131 AC: 2 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000999 AC: 68 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000516 Hom.: 0

Bravo AF: 0.000484

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	-0.32
CADD	Benign	7.9
DANN	Benign	0.73
PhyloP100		-0.91
Mutation Taster		=99/1	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: rs183605922; hg19: chr2-219498880; COSMIC: COSV68743159; COSMIC: COSV68743159;