chr14-64914442-G-A

Position:

• chr14-64914442-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001202559.1(CHURC1-FNTB):​c.28G>A​(p.Glu10Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CHURC1-FNTB NM_001202559.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

Genes affected

CHURC1-FNTB (HGNC:):

CHURC1 (HGNC:20099): (churchill domain containing 1) Predicted to enable zinc ion binding activity. Predicted to be involved in positive regulation of transcription, DNA-templated. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHURC1-FNTB	NM_001202559.1	c.28G>A	p.Glu10Lys	missense_variant	1/14
CHURC1	NM_001386928.1			upstream_gene_variant		ENST00000549115.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHURC1	ENST00000549115.7			upstream_gene_variant		1	NM_001386928.1	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 17, 2022

The c.28G>A (p.E10K) alteration is located in exon 1 (coding exon 1) of the CHURC1 gene. This alteration results from a G to A substitution at nucleotide position 28, causing the glutamic acid (E) at amino acid position 10 to be replaced by a lysine (K). 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	0.11
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.016	T;.;.
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.79	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.0	N;N;N
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.54	N;.;N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D;.;D
Sift4G	Pathogenic	0.0	D;D;D
Vest4		0.62
MutPred		0.34		Gain of catalytic residue at E10 (P = 0.0012);Gain of catalytic residue at E10 (P = 0.0012);Gain of catalytic residue at E10 (P = 0.0012);
MVP		0.36
MPC		0.75
ClinPred		0.81	D
GERP RS		5.0
Varity_R		0.41
gMVP		0.24

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: chr14-65381160;