rs2241617

Positions:

• chr16-87407442-T-C

Variant summary

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

The NM_015144.3(ZCCHC14):​c.*2838A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,208 control chromosomes in the GnomAD database, including 1,688 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 0.12 (1688 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZCCHC14 NM_015144.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZCCHC14	NM_015144.3	c.*2838A>G		3_prime_UTR_variant	13/13	ENST00000671377.2	NP_055959.2
ZCCHC14	XR_243401.4	n.6649+236A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZCCHC14	ENST00000671377.2	c.*2838A>G		3_prime_UTR_variant	13/13		NM_015144.3	ENSP00000499622	P1
ZCCHC14	ENST00000268616.9	c.*2838A>G		3_prime_UTR_variant	13/13	1		ENSP00000268616
ZCCHC14	ENST00000568020.6	c.*2602+236A>G		intron_variant, NMD_transcript_variant		1		ENSP00000455431

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18345 AN: 152090 Hom.: 1677 Cov.: 33

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.146

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.121 AC: 18372 AN: 152208 Hom.: 1688 Cov.: 33 AF XY: 0.129 AC XY: 9572 AN XY: 74404

Gnomad4 AFR AF: 0.0431

Gnomad4 AMR AF: 0.227

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.148

Alfa AF: 0.122 Hom.: 1813

Bravo AF: 0.129

Asia WGS AF: 0.279 AC: 967 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.71
DANN	Benign	0.82

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: rs2241617; hg19: chr16-87441048;