6-143886066-A-G

Variant names:

• chr6-143886066-A-G
• rs1032838829
• NM_001013623.3:c.125A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013623.3(ZC2HC1B):​c.125A>G​(p.Asn42Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N42T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZC2HC1B NM_001013623.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06921443).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013623.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC2HC1B	NM_001013623.3	MANE Select	c.125A>G	p.Asn42Ser	missense	Exon 3 of 8	NP_001013645.1	Q5TFG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZC2HC1B	ENST00000237275.9	TSL:1 MANE Select	c.125A>G	p.Asn42Ser	missense	Exon 3 of 8	ENSP00000237275.6	Q5TFG8
	ENSG00000280148	ENST00000454207.2	TSL:2	n.*69A>G		non_coding_transcript_exon	Exon 5 of 10	ENSP00000400756.2	A0A075B6Q4
	ZC2HC1B	ENST00000539295.3	TSL:1	n.312A>G		non_coding_transcript_exon	Exon 4 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.054
Sift	Benign	0.33	T
Sift4G	Benign	0.57	T
Polyphen		0.030	B
Vest4		0.12
MutPred		0.21		Gain of phosphorylation at N42 (P = 0.0123)
MVP		0.17
ClinPred		0.38	T
GERP RS		5.4
Varity_R		0.12
gMVP		0.078
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs1032838829; hg19: chr6-144207203;