chr21-46324204-G-C

Variant names:

• chr21-46324204-G-C
• rs202239640
• NM_006031.6:c.-25G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006031.6(PCNT):​c.-25G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000275 in 1,604,548 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 35)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: PCNT NM_006031.6 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.957
• Publications: 1 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]

C21orf58 (HGNC:1300): (chromosome 21 open reading frame 58)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 21-46324204-G-C is Benign according to our data. Variant chr21-46324204-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 340458.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0015 (228/152316) while in subpopulation AFR AF = 0.00532 (221/41566). AF 95% confidence interval is 0.00474. There are 2 homozygotes in GnomAd4. There are 95 alleles in the male GnomAd4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.-25G>C		5_prime_UTR	Exon 1 of 47	NP_006022.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNT	ENST00000359568.10	TSL:1 MANE Select	c.-25G>C		5_prime_UTR	Exon 1 of 47	ENSP00000352572.5	O95613-1
	PCNT	ENST00000695558.1		c.-25G>C		5_prime_UTR	Exon 1 of 48	ENSP00000512015.1	A0A8Q3SHZ3
	PCNT	ENST00000695526.1		c.-25G>C		5_prime_UTR	Exon 1 of 15	ENSP00000511988.1	A0A8Q3SHV6

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 229 AN: 152198 Hom.: 2 Cov.: 35

Gnomad AFR AF: 0.00536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000467 AC: 109 AN: 233596 AF XY: 0.000315

Gnomad AFR exome AF: 0.00714

Gnomad AMR exome AF: 0.0000907

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.000352

GnomAD4 exome AF: 0.000147 AC: 213 AN: 1452232 Hom.: 0 Cov.: 30 AF XY: 0.000132 AC XY: 95 AN XY: 721936

African (AFR) AF: 0.00555 AC: 185 AN: 33360

American (AMR) AF: 0.0000918 AC: 4 AN: 43568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25850

East Asian (EAS) AF: 0.00 AC: 0 AN: 39426

South Asian (SAS) AF: 0.00 AC: 0 AN: 84770

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52414

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5736

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107162

Other (OTH) AF: 0.000350 AC: 21 AN: 59946

GnomAD4 genome AF: 0.00150 AC: 228 AN: 152316 Hom.: 2 Cov.: 35 AF XY: 0.00128 AC XY: 95 AN XY: 74494

African (AFR) AF: 0.00532 AC: 221 AN: 41566

American (AMR) AF: 0.000392 AC: 6 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00137 Hom.: 0

Bravo AF: 0.00178

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Microcephalic osteodysplastic primordial dwarfism type II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.33
PhyloP100		0.96
PromoterAI		0.025	Neutral
Mutation Taster		=261/39	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: rs202239640; hg19: chr21-47744118;