chr16-68563440-A-G

Variant names:

• chr16-68563440-A-G
• NM_001305203.2:c.653A>G

Variant summary

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

The NM_001305203.2(ZFP90):​c.653A>G​(p.Lys218Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFP90 NM_001305203.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98

Genes affected

ZFP90 (HGNC:23329): (ZFP90 zinc finger protein) This gene encodes a member of the zinc finger protein family that modulates gene expression. The encoded protein derepresses the transcription of certain fetal cardiac genes and may contribute to the genetic reprogramming that occurs during the development of heart failure. Genome wide association studies have identified this gene among ulcerative colitis risk loci. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP90	NM_001305203.2	c.653A>G	p.Lys218Arg	missense_variant	Exon 5 of 5	ENST00000563169.7	NP_001292132.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP90	ENST00000563169.7	c.653A>G	p.Lys218Arg	missense_variant	Exon 5 of 5	1	NM_001305203.2	ENSP00000454418.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461276 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726920

Gnomad4 AFR exome AF: 0.00

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.653A>G (p.K218R) alteration is located in exon 4 (coding exon 4) of the ZFP90 gene. This alteration results from a A to G substitution at nucleotide position 653, causing the lysine (K) at amino acid position 218 to be replaced by an arginine (R). 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	0.14
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T;T;T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.64	.;.;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.56	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.1	M;M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.4	.;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.016	.;D;D
Sift4G	Uncertain	0.017	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.43
MutPred		0.53		Loss of methylation at K218 (P = 0.0011);Loss of methylation at K218 (P = 0.0011);Loss of methylation at K218 (P = 0.0011);
MVP		0.70
MPC		0.24
ClinPred		0.91	D
GERP RS		5.0
Varity_R		0.16
gMVP		0.14

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: chr16-68597343;