NM_001305203.2:c.449C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001305203.2(ZFP90):​c.449C>T​(p.Thr150Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: ZFP90 NM_001305203.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022070318).

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>T	p.Thr150Ile	missense	Exon 5 of 5	NP_001292132.1	Q8TF47-1
	ZFP90	NM_133458.4		c.449C>T	p.Thr150Ile	missense	Exon 5 of 5	NP_597715.2	Q8TF47-1
	ZFP90	NM_001305206.2		c.*222C>T		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>T	p.Thr150Ile	missense	Exon 5 of 5	ENSP00000454418.2	Q8TF47-1
	ZFP90	ENST00000570495.5	TSL:1	c.449C>T	p.Thr150Ile	missense	Exon 5 of 5	ENSP00000460547.1	Q8TF47-1
	ZFP90	ENST00000611381.4	TSL:1	c.256+4668C>T		intron	N/A	ENSP00000480309.1	Q8TF47-3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000157 AC: 39 AN: 248590 AF XY: 0.000193

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000424 AC: 62 AN: 1461232 Hom.: 0 Cov.: 32 AF XY: 0.0000468 AC XY: 34 AN XY: 726902

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

American (AMR) AF: 0.00 AC: 0 AN: 44560

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

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39694

South Asian (SAS) AF: 0.000267 AC: 23 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: 0.0000171 AC: 19 AN: 1111792

Other (OTH) AF: 0.0000166 AC: 1 AN: 60360

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152176 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74326

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

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.000384 AC: 2 AN: 5206

South Asian (SAS) AF: 0.000414 AC: 2 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: 0.0000294 AC: 2 AN: 68026

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

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.000166 AC: 20

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.7
DANN	Benign	0.96
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.000090	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.58
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.028
Sift	Benign	0.12	T
Sift4G	Benign	0.16	T
Polyphen		0.0040	B
Vest4		0.089
MutPred		0.33		Loss of ubiquitination at K147 (P = 0.0487)
MVP		0.55
MPC		0.12
ClinPred		0.014	T
GERP RS		3.5
Varity_R		0.067
gMVP		0.42
Mutation Taster		=93/7	polymorphism

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;