NM_001305203.2:c.71C>T

Variant names:

• chr16-68558035-C-T
• rs1287309187
• NM_001305203.2:c.71C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001305203.2(ZFP90):​c.71C>T​(p.Thr24Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
• Consequence: ZFP90 NM_001305203.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.885
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.71C>T	p.Thr24Ile	missense	Exon 3 of 5	NP_001292132.1	Q8TF47-1
	ZFP90	NM_133458.4		c.71C>T	p.Thr24Ile	missense	Exon 3 of 5	NP_597715.2	Q8TF47-1
	ZFP90	NM_001305204.2		c.71C>T	p.Thr24Ile	missense	Exon 3 of 5	NP_001292133.1	Q8TF47-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP90	ENST00000563169.7	TSL:1 MANE Select	c.71C>T	p.Thr24Ile	missense	Exon 3 of 5	ENSP00000454418.2	Q8TF47-1
	ZFP90	ENST00000570495.5	TSL:1	c.71C>T	p.Thr24Ile	missense	Exon 3 of 5	ENSP00000460547.1	Q8TF47-1
	ZFP90	ENST00000611381.4	TSL:1	c.71C>T	p.Thr24Ile	missense	Exon 3 of 5	ENSP00000480309.1	Q8TF47-3

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151842 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151842 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74112

African (AFR) AF: 0.0000242 AC: 1 AN: 41286

American (AMR) AF: 0.00 AC: 0 AN: 15238

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

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	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		0.89
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.1	D
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.77
MutPred		0.75		Gain of catalytic residue at T24 (P = 0.0279)
MVP		0.64
MPC		0.57
ClinPred		0.99	D
GERP RS		5.5
PromoterAI		-0.00010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.42
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs1287309187; hg19: chr16-68591938;