NM_006031.6:c.7354G>A

Variant names:

• chr21-46427655-G-A
• NM_006031.6:c.7354G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006031.6(PCNT):​c.7354G>A​(p.Asp2452Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PCNT NM_006031.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38

Genes affected

PCNT (HGNC:16068): (pericentrin) The protein encoded by this gene binds to calmodulin and is expressed in the centrosome. It is an integral component of the pericentriolar material (PCM). The protein contains a series of coiled-coil domains and a highly conserved PCM targeting motif called the PACT domain near its C-terminus. The protein interacts with the microtubule nucleation component gamma-tubulin and is likely important to normal functioning of the centrosomes, cytoskeleton, and cell-cycle progression. Mutations in this gene cause Seckel syndrome-4 and microcephalic osteodysplastic primordial dwarfism type II. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10998258).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNT	NM_006031.6	c.7354G>A	p.Asp2452Asn	missense_variant	Exon 34 of 47	ENST00000359568.10	NP_006022.3
PCNT	NM_001315529.2	c.7000G>A	p.Asp2334Asn	missense_variant	Exon 34 of 47		NP_001302458.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNT	ENST00000359568.10	c.7354G>A	p.Asp2452Asn	missense_variant	Exon 34 of 47	1	NM_006031.6	ENSP00000352572.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461636 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727114

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.34	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.075
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.20	B
Vest4		0.19
MutPred		0.35		Gain of helix (P = 0.0225);
MVP		0.47
MPC		0.080
ClinPred		0.25	T
GERP RS		2.6
Varity_R		0.057
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-47847569;