3-196707572-T-C

Position:

• chr3-196707572-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_032898.5(CEP19):​c.471A>G​(p.Thr157=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 1,610,680 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (27 hom.)
• Consequence: CEP19 NM_032898.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0170

Genes affected

CEP19 (HGNC:28209): (centrosomal protein 19) The protein encoded by this gene localizes to centrosomes and primary cilia and co-localizes with a marker for the mother centriole. This gene resides in a region of human chromosome 3 that is linked to morbid obesity. A homozygous knockout of the orthologous gene in mouse resulted in mice with morbid obesity, hyperphagy, glucose intolerance, and insulin resistance. Mutations in this gene cause morbid obesity and spermatogenic failure (MOSPGF). This gene has a pseudogene on human chromosome 2. [provided by RefSeq, Apr 2014]

PIGX (HGNC:26046): (phosphatidylinositol glycan anchor biosynthesis class X) This gene encodes a type I transmembrane protein in the endoplasmic reticulum (ER). The protein is an essential component of glycosylphosphatidylinositol-mannosyltransferase I, which transfers the first of the four mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis. Studies in rat indicate that the protein is translated from a non-AUG translation initiation site. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 3-196707572-T-C is Benign according to our data. Variant chr3-196707572-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 719485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.017 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP19	NM_032898.5	c.471A>G	p.Thr157=	synonymous_variant	3/3	ENST00000409690.5	NP_116287.3
CEP19	NM_001379469.1	c.471A>G	p.Thr157=	synonymous_variant	3/3		NP_001366398.1
CEP19	NM_001379470.1	c.471A>G	p.Thr157=	synonymous_variant	3/3		NP_001366399.1
CEP19	NM_001379468.1	c.366A>G	p.Thr122=	synonymous_variant	2/2		NP_001366397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP19	ENST00000409690.5	c.471A>G	p.Thr157=	synonymous_variant	3/3	1	NM_032898.5	ENSP00000387209	P1
CEP19	ENST00000399942.4	c.366A>G	p.Thr122=	synonymous_variant	2/2	5		ENSP00000382823
PIGX	ENST00000426755.5	c.-11-9286T>C		intron_variant		3		ENSP00000409073

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 562 AN: 152202 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00617

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00381 AC: 944 AN: 247584 Hom.: 7 AF XY: 0.00375 AC XY: 504 AN XY: 134440

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.000641

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00585

Gnomad NFE exome AF: 0.00675

Gnomad OTH exome AF: 0.00383

GnomAD4 exome AF: 0.00541 AC: 7883 AN: 1458360 Hom.: 27 Cov.: 31 AF XY: 0.00517 AC XY: 3749 AN XY: 725382

Gnomad4 AFR exome AF: 0.000988

Gnomad4 AMR exome AF: 0.000808

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00591

Gnomad4 NFE exome AF: 0.00657

Gnomad4 OTH exome AF: 0.00333

GnomAD4 genome AF: 0.00369 AC: 562 AN: 152320 Hom.: 1 Cov.: 32 AF XY: 0.00329 AC XY: 245 AN XY: 74486

Gnomad4 AFR AF: 0.00127

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.00617

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00473 Hom.: 2

Bravo AF: 0.00339

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00534

EpiControl AF: 0.00528

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	CEP19: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.0
DANN	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs142469317; hg19: chr3-196434443;