16-4361058-C-T

Variant names:

• chr16-4361058-C-T
• rs773483699
• NM_024535.5:c.1802G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

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]

ACMG classification

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
CORO7	NM_024535.5	c.1802G>A	p.Arg601His	missense_variant	Exon 19 of 28	ENST00000251166.9	NP_078811.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORO7	ENST00000251166.9	c.1802G>A	p.Arg601His	missense_variant	Exon 19 of 28	1	NM_024535.5	ENSP00000251166.4
CORO7-PAM16	ENST00000572467.5	c.1802G>A	p.Arg601His	missense_variant	Exon 19 of 31	2		ENSP00000460885.1

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152220 Hom.: 0 Cov.: 32

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

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

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

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

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

Other links and lift over

dbSNP: rs773483699; hg19: chr16-4411059;