6-31145711-C-A

Position:

• chr6-31145711-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001105564.2(CCHCR1):​c.1678G>T​(p.Val560Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.24

Genes affected

CCHCR1 (HGNC:13930): (coiled-coil alpha-helical rod protein 1) This gene encodes a protein with five coiled-coil alpha-helical rod domains that is thought to act as a regulator of mRNA metabolism through its interaction with mRNA-decapping protein 4. It localizes to P-bodies, the site of mRNA metabolism, with an N-terminus that is required for this subcellular localization, suggesting it is a P-body component. Naturally occurring mutations in this gene are associated with psoriasis. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCHCR1	NM_001105564.2	c.1678G>T	p.Val560Phe	missense_variant	11/18	ENST00000396268.8	NP_001099034.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCHCR1	ENST00000396268.8	c.1678G>T	p.Val560Phe	missense_variant	11/18	1	NM_001105564.2	ENSP00000379566	A2

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

Mar 31, 2024

The c.1678G>T (p.V560F) alteration is located in exon 11 (coding exon 11) of the CCHCR1 gene. This alteration results from a G to T substitution at nucleotide position 1678, causing the valine (V) at amino acid position 560 to be replaced by a phenylalanine (F). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	.;T;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.90	.;.;D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.
MutationTaster	Benign	0.65	D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.24
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.12	T;T;T
Polyphen		0.99	D;D;.
Vest4		0.91
MutPred		0.63		.;Gain of methylation at K470 (P = 0.1102);.;
MVP		0.49
MPC		1.5
ClinPred		0.91	D
GERP RS		2.8
Varity_R		0.090
gMVP		0.77

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: chr6-31113488;