rs61735817

Variant names:

• chr21-46427786-C-T
• rs61735817
• NM_006031.6:c.7485C>T

Your query was ambiguous. Multiple possible variants found:

• chr21-46427786-C-T
• chr21-46427786-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006031.6(PCNT):​c.7485C>T​(p.Ile2495Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 1,613,372 control chromosomes in the GnomAD database, including 2,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (194 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2418 hom.)
• Consequence: PCNT NM_006031.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.02
• Publications: 12 publications found

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]

PCNT Gene-Disease associations (from GenCC):

• microcephalic osteodysplastic primordial dwarfism type II

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet
• Moyamoya disease

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 21-46427786-C-T is Benign according to our data. Variant chr21-46427786-C-T is described in ClinVar as Benign. ClinVar VariationId is 138602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.02 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006031.6. 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
	PCNT	NM_006031.6	MANE Select	c.7485C>T	p.Ile2495Ile	synonymous	Exon 34 of 47	NP_006022.3
	PCNT	NM_001315529.2		c.7131C>T	p.Ile2377Ile	synonymous	Exon 34 of 47	NP_001302458.1	O95613-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	ENST00000359568.10	TSL:1 MANE Select	c.7485C>T	p.Ile2495Ile	synonymous	Exon 34 of 47	ENSP00000352572.5	O95613-1
	PCNT	ENST00000480896.5	TSL:1	c.7131C>T	p.Ile2377Ile	synonymous	Exon 34 of 47	ENSP00000511989.1	O95613-2
	PCNT	ENST00000695558.1		c.7518C>T	p.Ile2506Ile	synonymous	Exon 35 of 48	ENSP00000512015.1	A0A8Q3SHZ3

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6312 AN: 152156 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.00982

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0567

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.0850

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.0383

GnomAD2 exomes AF: 0.0431 AC: 10804 AN: 250542 AF XY: 0.0430

Gnomad AFR exome AF: 0.00864

Gnomad AMR exome AF: 0.0180

Gnomad ASJ exome AF: 0.0572

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0863

Gnomad NFE exome AF: 0.0610

Gnomad OTH exome AF: 0.0460

GnomAD4 exome AF: 0.0537 AC: 78479 AN: 1461098 Hom.: 2418 Cov.: 33 AF XY: 0.0528 AC XY: 38345 AN XY: 726834

African (AFR) AF: 0.00786 AC: 263 AN: 33474

American (AMR) AF: 0.0197 AC: 882 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0558 AC: 1457 AN: 26132

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0138 AC: 1191 AN: 86250

European-Finnish (FIN) AF: 0.0832 AC: 4391 AN: 52772

Middle Eastern (MID) AF: 0.0243 AC: 139 AN: 5724

European-Non Finnish (NFE) AF: 0.0605 AC: 67292 AN: 1111962

Other (OTH) AF: 0.0474 AC: 2861 AN: 60372

GnomAD4 genome AF: 0.0414 AC: 6309 AN: 152274 Hom.: 194 Cov.: 32 AF XY: 0.0409 AC XY: 3043 AN XY: 74460

African (AFR) AF: 0.00979 AC: 407 AN: 41568

American (AMR) AF: 0.0260 AC: 398 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0567 AC: 197 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00892 AC: 43 AN: 4822

European-Finnish (FIN) AF: 0.0850 AC: 902 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0625 AC: 4253 AN: 68012

Other (OTH) AF: 0.0379 AC: 80 AN: 2112

Alfa AF: 0.0542 Hom.: 130

Bravo AF: 0.0359

Asia WGS AF: 0.00982 AC: 34 AN: 3478

EpiCase AF: 0.0542

EpiControl AF: 0.0535

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Microcephalic osteodysplastic primordial dwarfism type II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.39
DANN	Benign	0.42
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs61735817; hg19: chr21-47847700; COSMIC: COSV64033655; COSMIC: COSV64033655;