rs3748400

Variant names:

• chr16-87412233-C-A
• NM_015144.3:c.2488G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-87412233-C-A
• chr16-87412233-C-T

Variant summary

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

The NM_015144.3(ZCCHC14):​c.2488G>T​(p.Val830Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZCCHC14 NM_015144.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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 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=0.2604785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZCCHC14	NM_015144.3	c.2488G>T	p.Val830Leu	missense_variant	Exon 12 of 13	ENST00000671377.2	NP_055959.2
ZCCHC14	XM_005255858.4	c.2488G>T	p.Val830Leu	missense_variant	Exon 12 of 12		XP_005255915.3
ZCCHC14	XM_017023082.3	c.1969G>T	p.Val657Leu	missense_variant	Exon 12 of 12		XP_016878571.1
ZCCHC14	XR_243401.4	n.3274G>T		non_coding_transcript_exon_variant	Exon 12 of 14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZCCHC14	ENST00000671377.2	c.2488G>T	p.Val830Leu	missense_variant	Exon 12 of 13		NM_015144.3	ENSP00000499622.1
ZCCHC14	ENST00000268616.9	c.2077G>T	p.Val693Leu	missense_variant	Exon 12 of 13	1		ENSP00000268616.4
ZCCHC14	ENST00000568020.6	n.2107G>T		non_coding_transcript_exon_variant	Exon 12 of 14	1		ENSP00000455431.2
ZCCHC14	ENST00000561928.1	c.1726G>T	p.Val576Leu	missense_variant	Exon 10 of 10	5		ENSP00000456499.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461698 Hom.: 0 Cov.: 96 AF XY: 0.00 AC XY: 0 AN XY: 727164

Gnomad4 AFR exome AF: 0.0000299

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.029	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.32	T
Polyphen		0.99	D
Vest4		0.18
MutPred		0.16		Gain of sheet (P = 0.1945);
MVP		0.068
MPC		0.27
ClinPred		0.76	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.30
gMVP		0.36

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: chr16-87445839;