GeneBe

NM_022909.4:c.591C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_022909.4(CENPH):​c.591C>A​(p.Ile197Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CENPH
NM_022909.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.140

Publications

0 publications found
Variant links:
Genes affected
CENPH (HGNC:17268): (centromere protein H) Centromere and kinetochore proteins play a critical role in centromere structure, kinetochore formation, and sister chromatid separation. The protein encoded by this gene colocalizes with inner kinetochore plate proteins CENP-A and CENP-C in both interphase and metaphase. It localizes outside of centromeric heterochromatin, where CENP-B is localized, and inside the kinetochore corona, where CENP-E is localized during prometaphase. It is thought that this protein can bind to itself, as well as to CENP-A, CENP-B or CENP-C. Multimers of the protein localize constitutively to the inner kinetochore plate and play an important role in the organization and function of the active centromere-kinetochore complex. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (REVEL=0.031).
BP7
Synonymous conserved (PhyloP=0.14 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CENPHNM_022909.4 linkc.591C>A p.Ile197Ile synonymous_variant Exon 8 of 9 ENST00000283006.7 NP_075060.1 Q9H3R5A0A0S2Z5T0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CENPHENST00000283006.7 linkc.591C>A p.Ile197Ile synonymous_variant Exon 8 of 9 1 NM_022909.4 ENSP00000283006.2 Q9H3R5
CENPHENST00000515001.5 linkc.534C>A p.Ile178Ile synonymous_variant Exon 7 of 8 2 ENSP00000426014.1 B3KVZ3
CENPHENST00000502689.1 linkc.408C>A p.Ile136Ile synonymous_variant Exon 7 of 8 5 ENSP00000423936.1 H0Y9E6
CENPHENST00000510742.1 linkn.569C>A non_coding_transcript_exon_variant Exon 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1448138
Hom.:
0
Cov.:
26
AF XY:
0.00
AC XY:
0
AN XY:
721410
African (AFR)
AF:
0.00
AC:
0
AN:
33132
American (AMR)
AF:
0.00
AC:
0
AN:
44598
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26036
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39546
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85794
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53392
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5738
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1099928
Other (OTH)
AF:
0.00
AC:
0
AN:
59974
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
8.0
DANN
Benign
0.51
PhyloP100
0.14

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

Publications

Other links and lift over

dbSNP: rs1212157695; hg19: chr5-68504126; API