16-30185212-G-A

Variant names:

• chr16-30185212-G-A
• NM_007074.4:c.3G>A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_Supporting PM2 PP5_Moderate

The NM_007074.4(CORO1A):​c.3G>A​(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CORO1A NM_007074.4 start_lost
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 5.49

Genes affected

CORO1A (HGNC:2252): (coronin 1A) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Alternative splicing results in multiple transcript variants. A related pseudogene has been defined on chromosome 16. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 107 codons. Genomic position: 30186718. Lost 0.230 part of the original CDS.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-30185212-G-A is Pathogenic according to our data. Variant chr16-30185212-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 3658357.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CORO1A	NM_007074.4	c.3G>A	p.Met1?	start_lost	Exon 2 of 11	ENST00000219150.10	NP_009005.1
CORO1A	NM_001193333.3	c.3G>A	p.Met1?	start_lost	Exon 3 of 12		NP_001180262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CORO1A	ENST00000219150.10	c.3G>A	p.Met1?	start_lost	Exon 2 of 11	1	NM_007074.4	ENSP00000219150.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Severe combined immunodeficiency due to CORO1A deficiency Pathogenic:1

Jun 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change affects the initiator methionine of the CORO1A mRNA. The next in-frame methionine is located at codon 107. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CORO1A-related conditions. This variant disrupts a region of the CORO1A protein in which other variant(s) (p.Arg12Leu) have been determined to be pathogenic (PMID: 25666293; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T;.;D;D;T;.;T;T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;T;.;D;D;D;D;D
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.99	D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.11	D
PROVEAN	Uncertain	-2.4	N;D;N;N;N;N;N;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D
Polyphen		1.0	.;.;D;D;.;.;.;.
Vest4		0.80, 0.81
MutPred		0.98		Gain of catalytic residue at M1 (P = 0.0271);.;Gain of catalytic residue at M1 (P = 0.0271);Gain of catalytic residue at M1 (P = 0.0271);Gain of catalytic residue at M1 (P = 0.0271);Gain of catalytic residue at M1 (P = 0.0271);Gain of catalytic residue at M1 (P = 0.0271);Gain of catalytic residue at M1 (P = 0.0271);
MVP		0.84
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.67
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-30196533;