rs11556924

Variant names:

• chr7-130023656-C-A
• rs11556924
• NM_016478.5:c.1088G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-130023656-C-A
• chr7-130023656-C-T

Variant summary

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

The NM_016478.5(ZC3HC1):​c.1088G>T​(p.Arg363Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R363C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ZC3HC1 NM_016478.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 232 publications found

Genes affected

ZC3HC1 (HGNC:29913): (zinc finger C3HC-type containing 1) This gene encodes an F-box-containing protein that is a component of an SCF-type E3 ubiquitin ligase complex that regulates the onset of cell division. The G2/M transition in the cell cycle requires the interaction of the proteins cyclin B1 and cyclin-dependent kinase 1. The activated ubiquitin ligase complex targets the protein cyclin B1 for degradation, preventing this transition to mitosis. [provided by RefSeq, Aug 2013]

UBE2H-DT (HGNC:55615): (UBE2H divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
ZC3HC1	NM_016478.5	c.1088G>T	p.Arg363Leu	missense_variant	Exon 8 of 10	ENST00000358303.9	NP_057562.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3HC1	ENST00000358303.9	c.1088G>T	p.Arg363Leu	missense_variant	Exon 8 of 10	1	NM_016478.5	ENSP00000351052.4
ZC3HC1	ENST00000481503.5	c.959G>T	p.Arg320Leu	missense_variant	Exon 8 of 10	5		ENSP00000418533.1
ZC3HC1	ENST00000467642.5	n.*972G>T		non_coding_transcript_exon_variant	Exon 9 of 11	2		ENSP00000419509.1
ZC3HC1	ENST00000470651.2	n.*1041G>T		non_coding_transcript_exon_variant	Exon 9 of 11	4		ENSP00000420068.1
ZC3HC1	ENST00000484432.2	n.*902G>T		non_coding_transcript_exon_variant	Exon 8 of 10	4		ENSP00000417217.1
ZC3HC1	ENST00000648450.1	n.*1098G>T		non_coding_transcript_exon_variant	Exon 10 of 12			ENSP00000498166.1
ZC3HC1	ENST00000467642.5	n.*972G>T		3_prime_UTR_variant	Exon 9 of 11	2		ENSP00000419509.1
ZC3HC1	ENST00000470651.2	n.*1041G>T		3_prime_UTR_variant	Exon 9 of 11	4		ENSP00000420068.1
ZC3HC1	ENST00000484432.2	n.*902G>T		3_prime_UTR_variant	Exon 8 of 10	4		ENSP00000417217.1
ZC3HC1	ENST00000648450.1	n.*1098G>T		3_prime_UTR_variant	Exon 10 of 12			ENSP00000498166.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251378 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461884 Hom.: 0 Cov.: 48 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112006

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;.;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.2	M;.;.
PhyloP100		2.0
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.0050	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.62
MutPred		0.22		Gain of catalytic residue at R363 (P = 0.0094);.;.;
MVP		0.65
MPC		0.88
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.29
gMVP		0.33
Mutation Taster		=89/11	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: rs11556924; hg19: chr7-129663496;