chr6-149451016-G-T

Position:

• chr6-149451016-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207360.3(ZC3H12D):​c.1251C>A​(p.His417Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,303,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: ZC3H12D NM_207360.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0470

Genes affected

ZC3H12D (HGNC:21175): (zinc finger CCCH-type containing 12D) Predicted to enable endoribonuclease activity and mRNA binding activity. Involved in negative regulation of G1/S transition of mitotic cell cycle and negative regulation of cell growth. Located in P-body and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081618845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZC3H12D	NM_207360.3	c.1251C>A	p.His417Gln	missense_variant	6/6	ENST00000409806.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZC3H12D	ENST00000409806.8	c.1251C>A	p.His417Gln	missense_variant	6/6	1	NM_207360.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1303988 Hom.: 0 Cov.: 30 AF XY: 0.00000157 AC XY: 1 AN XY: 636154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.59e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.1251C>A (p.H417Q) alteration is located in exon 6 (coding exon 5) of the ZC3H12D gene. This alteration results from a C to A substitution at nucleotide position 1251, causing the histidine (H) at amino acid position 417 to be replaced by a glutamine (Q). 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	0.080
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.9
DANN	Benign	0.94
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.19	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.0070
Sift	Benign	0.14	T
Sift4G	Benign	0.085	T
Polyphen		0.012	B
Vest4		0.083
MutPred		0.41		Gain of solvent accessibility (P = 0.0081);
MVP		0.043
MPC		1.0
ClinPred		0.065	T
GERP RS		1.1
Varity_R		0.047
gMVP		0.095

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: chr6-149772152; COSMIC: COSV101116999; COSMIC: COSV101116999;