1-31310125-G-A

Position:

• chr1-31310125-G-A

Variant summary

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

The NM_016505.4(ZCCHC17):​c.27G>A​(p.Met9Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: ZCCHC17 NM_016505.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

Genes affected

ZCCHC17 (HGNC:30246): (zinc finger CCHC-type containing 17) Enables identical protein binding activity. Predicted to be involved in RNA stabilization. Predicted to be located in nucleolus. Predicted to be part of cytosolic large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
ZCCHC17	NM_016505.4	c.27G>A	p.Met9Ile	missense_variant	2/8	ENST00000344147.10	NP_057589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC17	ENST00000344147.10	c.27G>A	p.Met9Ile	missense_variant	2/8	1	NM_016505.4	ENSP00000343557.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000130 AC: 19 AN: 1461806 Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9 AN XY: 727202

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: 0.0000171

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.000109

EpiControl AF: 0.00

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

Sep 15, 2021

The c.27G>A (p.M9I) alteration is located in exon 2 (coding exon 1) of the ZCCHC17 gene. This alteration results from a G to A substitution at nucleotide position 27, causing the methionine (M) at amino acid position 9 to be replaced by an isoleucine (I). 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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0044	T;T;T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.78	T;.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.90	.;L;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.44	.;N;N
REVEL	Benign	0.045
Sift	Benign	0.075	.;T;T
Sift4G	Benign	0.15	T;T;T
Polyphen		0.0030	.;B;B
Vest4		0.56
MutPred		0.29		Loss of disorder (P = 0.0856);Loss of disorder (P = 0.0856);Loss of disorder (P = 0.0856);
MVP		0.55
MPC		0.087
ClinPred		0.72	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.40		Position offset: 39

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1375266425; hg19: chr1-31782972;