16-68563236-C-A

Variant names:

• chr16-68563236-C-A
• rs776621126
• NM_001305203.2:c.449C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001305203.2(ZFP90):​c.449C>A​(p.Thr150Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. T150I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZFP90 NM_001305203.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14885929).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305203.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP90	NM_001305203.2	MANE Select	c.449C>A	p.Thr150Lys	missense	Exon 5 of 5	NP_001292132.1	Q8TF47-1
	ZFP90	NM_133458.4		c.449C>A	p.Thr150Lys	missense	Exon 5 of 5	NP_597715.2	Q8TF47-1
	ZFP90	NM_001305206.2		c.*222C>A		3_prime_UTR	Exon 5 of 5	NP_001292135.1	J3QKQ8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP90	ENST00000563169.7	TSL:1 MANE Select	c.449C>A	p.Thr150Lys	missense	Exon 5 of 5	ENSP00000454418.2	Q8TF47-1
	ZFP90	ENST00000570495.5	TSL:1	c.449C>A	p.Thr150Lys	missense	Exon 5 of 5	ENSP00000460547.1	Q8TF47-1
	ZFP90	ENST00000611381.4	TSL:1	c.256+4668C>A		intron	N/A	ENSP00000480309.1	Q8TF47-3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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

GnomAD2 exomes AF: 0.00000805 AC: 2 AN: 248590 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000583

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461232 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726902

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.0000449 AC: 2 AN: 44560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111792

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74326

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.000458 AC: 7 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.5
DANN	Benign	0.89
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.00030	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.58
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.054
Sift	Uncertain	0.018	D
Sift4G	Benign	0.23	T
Polyphen		0.36	B
Vest4		0.34
MutPred		0.35		Gain of methylation at T150 (P = 0.0117)
MVP		0.60
MPC		0.16
ClinPred		0.066	T
GERP RS		3.5
Varity_R		0.11
gMVP		0.47

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

Other links and lift over

dbSNP: rs776621126; hg19: chr16-68597139;