16-4361058-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_024535.5(CORO7):​c.1802G>A​(p.Arg601His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000744 in 1,613,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

CORO7
NM_024535.5 missense

Scores

1
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72
Variant links:
Genes affected
CORO7 (HGNC:26161): (coronin 7) This gene encodes a member of the coronin protein family. However, unlike other coronin proteins, it is not an actin-binding protein but rather functions as an F-actin regulator directing anterograde Golgi to endosome transport. The encoded protein has two tandem WD-40 domain repeats and localizes to the trans-Golgi network. The protein undergoes K33-linked polyubiquitination via an E3 ligase complex. It is thought to play an essential role in maintenance of Golgi apparatus morphology. Alternative splicing results in multiple transcripts variants; some of which form read-through transcripts with a neighboring gene. [provided by RefSeq, Dec 2016]
CORO7-PAM16 (HGNC:44424): (CORO7-PAM16 readthrough) This locus represents naturally occurring read-through transcription between the neighboring CORO7 (coronin 7) and PAM16 (presequence translocase-associated motor 16) genes on chromosome 16. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jan 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3149697).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CORO7NM_024535.5 linkc.1802G>A p.Arg601His missense_variant Exon 19 of 28 ENST00000251166.9 NP_078811.3 P57737-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CORO7ENST00000251166.9 linkc.1802G>A p.Arg601His missense_variant Exon 19 of 28 1 NM_024535.5 ENSP00000251166.4 P57737-1
CORO7-PAM16ENST00000572467.5 linkc.1802G>A p.Arg601His missense_variant Exon 19 of 31 2 ENSP00000460885.1 A0A0A6YYL4

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152220
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000963
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000164
AC:
41
AN:
250026
Hom.:
0
AF XY:
0.000199
AC XY:
27
AN XY:
135574
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00190
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.0000780
AC:
114
AN:
1460992
Hom.:
0
Cov.:
35
AF XY:
0.0000771
AC XY:
56
AN XY:
726798
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000932
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.0000567
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000963
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000677
Hom.:
0
Bravo
AF:
0.0000642
ExAC
AF:
0.000115
AC:
14
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 01, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1802G>A (p.R601H) alteration is located in exon 19 (coding exon 19) of the CORO7 gene. This alteration results from a G to A substitution at nucleotide position 1802, causing the arginine (R) at amino acid position 601 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.22
CADD
Pathogenic
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.088
.;T;.;.
Eigen
Uncertain
0.45
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.80
D
M_CAP
Benign
0.077
D
MetaRNN
Benign
0.31
T;T;T;T
MetaSVM
Benign
-0.33
T
MutationAssessor
Benign
1.5
.;L;.;.
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-3.0
.;D;.;.
REVEL
Uncertain
0.43
Sift
Uncertain
0.010
.;D;.;.
Sift4G
Uncertain
0.025
D;T;D;D
Polyphen
1.0
.;D;.;D
Vest4
0.61
MutPred
0.71
Loss of catalytic residue at R601 (P = 0.0121);Loss of catalytic residue at R601 (P = 0.0121);.;.;
MVP
0.84
MPC
0.15
ClinPred
0.18
T
GERP RS
5.2
Varity_R
0.10
gMVP
0.47

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

LitVar

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

Other links and lift over

dbSNP: rs773483699; hg19: chr16-4411059; API