6-31145740-T-C

Position:

• chr6-31145740-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001105564.2(CCHCR1):​c.1649A>G​(p.Asn550Ser) 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 benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCHCR1 NM_001105564.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0710

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04285094).
• BP6: Variant 6-31145740-T-C is Benign according to our data. Variant chr6-31145740-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3264446.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCHCR1	NM_001105564.2	c.1649A>G	p.Asn550Ser	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.1649A>G	p.Asn550Ser	missense_variant	11/18	1	NM_001105564.2	ENSP00000379566	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.048
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.4
DANN	Benign	0.62
DEOGEN2	Benign	0.0026	.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.62	.;.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.64	.;N;.
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.65	N;N;N
REVEL	Benign	0.050
Sift	Benign	1.0	T;T;T
Sift4G	Benign	0.77	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.10
MutPred		0.26		.;Gain of phosphorylation at N461 (P = 0.0805);.;
MVP		0.067
MPC		0.34
ClinPred		0.029	T
GERP RS		0.67
Varity_R		0.019
gMVP		0.075

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr6-31113517;