22-41944504-C-T

Position:

• chr22-41944504-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024053.5(CENPM):​c.310+721G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 245,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0034 (0 hom.)
• Consequence: CENPM NM_024053.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165

Genes affected

CENPM (HGNC:18352): (centromere protein M) The protein encoded by this gene is an inner protein of the kinetochore, the multi-protein complex that binds spindle microtubules to regulate chromosome segregation during cell division. It belongs to the constitutive centromere-associated network protein group, whose members interact with outer kinetochore proteins and help to maintain centromere identity at each cell division cycle. The protein is structurally related to GTPases but cannot bind guanosine triphosphate. A point mutation that affects interaction with another constitutive centromere-associated network protein, CENP-I, impairs kinetochore assembly and chromosome alignment, suggesting that it is required for kinetochore formation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CENPM	NM_024053.5	c.310+721G>A		intron_variant		ENST00000215980.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CENPM	ENST00000215980.10	c.310+721G>A		intron_variant		1	NM_024053.5	P1

Frequencies

GnomAD3 genomes AF: 0.00210 AC: 315 AN: 150312 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000493

Gnomad AMI AF: 0.0398

Gnomad AMR AF: 0.00120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000396

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00339

Gnomad OTH AF: 0.00338

GnomAD4 exome AF: 0.00340 AC: 324 AN: 95192 Hom.: 0 AF XY: 0.00335 AC XY: 153 AN XY: 45694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00114

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00360

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.00209 AC: 315 AN: 150392 Hom.: 0 Cov.: 30 AF XY: 0.00211 AC XY: 155 AN XY: 73292

Gnomad4 AFR AF: 0.000492

Gnomad4 AMR AF: 0.00120

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000396

Gnomad4 NFE AF: 0.00339

Gnomad4 OTH AF: 0.00336

Alfa AF: 0.000374 Hom.: 115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.6
DANN	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs1023497; hg19: chr22-42340508;