6-143886759-G-A

Variant names:

• chr6-143886759-G-A
• rs1777534409
• NM_001013623.3:c.287G>A

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.287G>A​(p.Cys96Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZC2HC1B NM_001013623.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56
• 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=0.16800448).

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.287G>A	p.Cys96Tyr	missense	Exon 4 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.287G>A	p.Cys96Tyr	missense	Exon 4 of 8	ENSP00000237275.6	Q5TFG8
	ENSG00000280148	ENST00000454207.2	TSL:2	n.*231G>A		non_coding_transcript_exon	Exon 6 of 10	ENSP00000400756.2	A0A075B6Q4
	ZC2HC1B	ENST00000539295.3	TSL:1	n.474G>A		non_coding_transcript_exon	Exon 5 of 9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397570 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689296

African (AFR) AF: 0.0000318 AC: 1 AN: 31420

American (AMR) AF: 0.00 AC: 0 AN: 35500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25144

East Asian (EAS) AF: 0.00 AC: 0 AN: 35560

South Asian (SAS) AF: 0.00 AC: 0 AN: 78964

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1078086

Other (OTH) AF: 0.00 AC: 0 AN: 57938

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Benign	0.65
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.031
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.56	T
Polyphen		0.84	P
Vest4		0.46
MutPred		0.33		Gain of phosphorylation at C96 (P = 0.0359)
MVP		0.18
ClinPred		0.17	T
GERP RS		2.8
Varity_R		0.12
gMVP		0.46
Mutation Taster		=288/12	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: rs1777534409; hg19: chr6-144207896;