6-143898596-G-C

Variant names:

• chr6-143898596-G-C
• NM_001013623.3:c.394G>C

Variant summary

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

The NM_001013623.3(ZC2HC1B):​c.394G>C​(p.Ala132Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC2HC1B NM_001013623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

Genes affected

ZC2HC1B (HGNC:21174): (zinc finger C2HC-type containing 1B) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000280148 (HGNC:):

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 rank	MANE	Protein	UniProt
ZC2HC1B	NM_001013623.3	c.394G>C	p.Ala132Pro	missense_variant	Exon 5 of 8	ENST00000237275.9	NP_001013645.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC2HC1B	ENST00000237275.9	c.394G>C	p.Ala132Pro	missense_variant	Exon 5 of 8	1	NM_001013623.3	ENSP00000237275.6
ENSG00000280148	ENST00000454207.2	n.*338G>C		non_coding_transcript_exon_variant	Exon 7 of 10	2		ENSP00000400756.2
ZC2HC1B	ENST00000539295.3	n.581G>C		non_coding_transcript_exon_variant	Exon 6 of 9	1
ENSG00000280148	ENST00000454207.2	n.*338G>C		3_prime_UTR_variant	Exon 7 of 10	2		ENSP00000400756.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.394G>C (p.A132P) alteration is located in exon 5 (coding exon 5) of the ZC2HC1B gene. This alteration results from a G to C substitution at nucleotide position 394, causing the alanine (A) at amino acid position 132 to be replaced by a proline (P). 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	0.24
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.36		Loss of helix (P = 0.0444);
MVP		0.18
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.88
gMVP		0.74

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: chr6-144219733;