rs1023497

Variant names:

• chr22-41944504-C-A
• rs1023497
• NM_024053.5:c.310+721G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-41944504-C-A
• chr22-41944504-C-G
• chr22-41944504-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_024053.5(CENPM):​c.310+721G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000403 in 245,594 control chromosomes in the GnomAD database, including 3 homozygotes. 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 0.00055 (3 hom., cov: 30)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: CENPM NM_024053.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000168 (16/95202) while in subpopulation EAS AF = 0.0279 (11/394). AF 95% confidence interval is 0.0157. There are 0 homozygotes in GnomAdExome4. There are 5 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPM	NM_024053.5	c.310+721G>T		intron_variant	Intron 4 of 5	ENST00000215980.10	NP_076958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPM	ENST00000215980.10	c.310+721G>T		intron_variant	Intron 4 of 5	1	NM_024053.5	ENSP00000215980.5

Frequencies

GnomAD3 genomes AF: 0.000552 AC: 83 AN: 150312 Hom.: 3 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0159

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.000168 AC: 16 AN: 95202 Hom.: 0 AF XY: 0.000109 AC XY: 5 AN XY: 45698

African (AFR) AF: 0.00 AC: 0 AN: 1558

American (AMR) AF: 0.00 AC: 0 AN: 106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 604

East Asian (EAS) AF: 0.0279 AC: 11 AN: 394

South Asian (SAS) AF: 0.00 AC: 0 AN: 1748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 182

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 87502

Other (OTH) AF: 0.00162 AC: 5 AN: 3078

GnomAD4 genome AF: 0.000552 AC: 83 AN: 150392 Hom.: 3 Cov.: 30 AF XY: 0.000682 AC XY: 50 AN XY: 73292

African (AFR) AF: 0.00 AC: 0 AN: 40648

American (AMR) AF: 0.00 AC: 0 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.0159 AC: 82 AN: 5152

South Asian (SAS) AF: 0.00 AC: 0 AN: 4774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67916

Other (OTH) AF: 0.000480 AC: 1 AN: 2084

Alfa AF: 0.00 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	3.9
DANN	Benign	0.82
PhyloP100		-0.17
Mutation Taster		=100/0	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: rs1023497; hg19: chr22-42340508;