rs9646303

Positions:

• chr16-87428363-G-A
• chr16-87428363-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015144.3(ZCCHC14):​c.769-4482C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 152,174 control chromosomes in the GnomAD database, including 53,807 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (53807 hom., cov: 32)
• Consequence: ZCCHC14 NM_015144.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZCCHC14	NM_015144.3	c.769-4482C>T		intron_variant		ENST00000671377.2
ZCCHC14	XM_005255858.4	c.769-4482C>T		intron_variant
ZCCHC14	XM_017023082.3	c.250-4482C>T		intron_variant
ZCCHC14	XR_243401.4	n.1555-4482C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZCCHC14	ENST00000671377.2	c.769-4482C>T		intron_variant			NM_015144.3	P1
ZCCHC14	ENST00000268616.9	c.358-4482C>T		intron_variant		1
ZCCHC14	ENST00000568020.6	c.390-4482C>T		intron_variant, NMD_transcript_variant		1
ZCCHC14	ENST00000561928.1	c.8-4482C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.837 AC: 127312 AN: 152056 Hom.: 53762 Cov.: 32

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.822

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.837 AC: 127408 AN: 152174 Hom.: 53807 Cov.: 32 AF XY: 0.829 AC XY: 61723 AN XY: 74414

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.838

Gnomad4 FIN AF: 0.855

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.821

Alfa AF: 0.856 Hom.: 99168

Bravo AF: 0.820

Asia WGS AF: 0.725 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.48
DANN	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs9646303; hg19: chr16-87461969;