16-87411912-T-C

Position:

• chr16-87411912-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015144.3(ZCCHC14):​c.2809A>G​(p.Ser937Gly) 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. 14/21 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)
• Consequence: ZCCHC14 NM_015144.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.502

Genes affected

ZCCHC14 (HGNC:24134): (zinc finger CCHC-type containing 14) Predicted to enable nucleic acid binding activity; phosphatidylinositol binding activity; and zinc ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.036673874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZCCHC14	NM_015144.3	c.2809A>G	p.Ser937Gly	missense_variant	12/13	ENST00000671377.2
ZCCHC14	XM_005255858.4	c.2809A>G	p.Ser937Gly	missense_variant	12/12
ZCCHC14	XM_017023082.3	c.2290A>G	p.Ser764Gly	missense_variant	12/12
ZCCHC14	XR_243401.4	n.3595A>G		non_coding_transcript_exon_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC14	ENST00000671377.2	c.2809A>G	p.Ser937Gly	missense_variant	12/13		NM_015144.3	P1
ZCCHC14	ENST00000268616.9	c.2398A>G	p.Ser800Gly	missense_variant	12/13	1
ZCCHC14	ENST00000568020.6	c.2431A>G	p.Ser811Gly	missense_variant, NMD_transcript_variant	12/14	1
ZCCHC14	ENST00000561928.1	c.2050A>G	p.Ser684Gly	missense_variant	10/10	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 94

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 05, 2023

The c.2398A>G (p.S800G) alteration is located in exon 12 (coding exon 12) of the ZCCHC14 gene. This alteration results from a A to G substitution at nucleotide position 2398, causing the serine (S) at amino acid position 800 to be replaced by a glycine (G). 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	0.060
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.1
DANN	Benign	0.79
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.081	N
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.89	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.056
Sift	Benign	0.22	T
Sift4G	Uncertain	0.050	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.16		Loss of glycosylation at S800 (P = 0.0063);
MVP		0.043
MPC		0.23
ClinPred		0.16	T
GERP RS		-0.50
Varity_R		0.045
gMVP		0.16

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: chr16-87445518;