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GeneBe

19-10393271-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_007065.4(CDC37):c.897G>A(p.Glu299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00552 in 1,612,926 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0055 ( 27 hom. )

Consequence

CDC37
NM_007065.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.630
Variant links:
Genes affected
CDC37 (HGNC:1735): (cell division cycle 37, HSP90 cochaperone) The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Sacchromyces cerevisiae. This protein is a molecular chaperone with specific function in cell signal transduction. It has been shown to form complex with Hsp90 and a variety of protein kinases including CDK4, CDK6, SRC, RAF-1, MOK, as well as eIF2 alpha kinases. It is thought to play a critical role in directing Hsp90 to its target kinases. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-10393271-C-T is Benign according to our data. Variant chr19-10393271-C-T is described in ClinVar as [Benign]. Clinvar id is 782051.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.63 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 855 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CDC37NM_007065.4 linkuse as main transcriptc.897G>A p.Glu299= synonymous_variant 6/8 ENST00000222005.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CDC37ENST00000222005.7 linkuse as main transcriptc.897G>A p.Glu299= synonymous_variant 6/81 NM_007065.4 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00562
AC:
855
AN:
152138
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000989
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.0265
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0225
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00675
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00584
AC:
1439
AN:
246280
Hom.:
7
AF XY:
0.00582
AC XY:
778
AN XY:
133588
show subpopulations
Gnomad AFR exome
AF:
0.00121
Gnomad AMR exome
AF:
0.00108
Gnomad ASJ exome
AF:
0.0183
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0201
Gnomad NFE exome
AF:
0.00669
Gnomad OTH exome
AF:
0.00647
GnomAD4 exome
AF:
0.00551
AC:
8045
AN:
1460670
Hom.:
27
Cov.:
32
AF XY:
0.00547
AC XY:
3974
AN XY:
726640
show subpopulations
Gnomad4 AFR exome
AF:
0.000777
Gnomad4 AMR exome
AF:
0.00103
Gnomad4 ASJ exome
AF:
0.0200
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0187
Gnomad4 NFE exome
AF:
0.00550
Gnomad4 OTH exome
AF:
0.00580
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00562
AC:
855
AN:
152256
Hom.:
6
Cov.:
32
AF XY:
0.00662
AC XY:
493
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.000986
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.0265
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0225
Gnomad4 NFE
AF:
0.00675
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00677
Hom.:
0
Bravo
AF:
0.00372
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00529
EpiControl
AF:
0.00486

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJun 04, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
12
Dann
Benign
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140381502; hg19: chr19-10503947; API