rs147590470

Variant names:

• chr16-11761474-T-A
• rs147590470
• NM_014153.4:c.2251A>T

Your query was ambiguous. Multiple possible variants found:

• chr16-11761474-T-A
• chr16-11761474-T-C

Variant summary

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

The NM_014153.4(ZC3H7A):​c.2251A>T​(p.Ile751Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I751V) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ZC3H7A NM_014153.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.858

Genes affected

ZC3H7A (HGNC:30959): (zinc finger CCCH-type containing 7A) Enables miRNA binding activity. Involved in production of miRNAs involved in gene silencing by miRNA. Predicted to be located in nucleus. [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=0.035844773).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZC3H7A	NM_014153.4	c.2251A>T	p.Ile751Phe	missense_variant	Exon 19 of 23	ENST00000355758.9	NP_054872.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZC3H7A	ENST00000355758.9	c.2251A>T	p.Ile751Phe	missense_variant	Exon 19 of 23	1	NM_014153.4	ENSP00000347999.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251394 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135858

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74334

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.69
DEOGEN2	Benign	0.0067	T;T;.
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.61
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.75	.;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.036	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.34	N;N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.74	N;N;.
REVEL	Benign	0.076
Sift	Benign	0.71	T;T;.
Sift4G	Benign	0.70	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.14
MutPred		0.29		Loss of methylation at K754 (P = 0.1016);Loss of methylation at K754 (P = 0.1016);.;
MVP		0.068
MPC		0.83
ClinPred		0.061	T
GERP RS		-0.89
Varity_R		0.025
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs147590470; hg19: chr16-11855330;