16-68563134-C-T

Variant names:

• chr16-68563134-C-T
• rs368733952
• NM_001305203.2:c.347C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001305203.2(ZFP90):​c.347C>T​(p.Thr116Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,838 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. 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. T116R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZFP90 NM_001305203.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06124404).

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.347C>T	p.Thr116Ile	missense	Exon 5 of 5	NP_001292132.1	Q8TF47-1
	ZFP90	NM_133458.4		c.347C>T	p.Thr116Ile	missense	Exon 5 of 5	NP_597715.2	Q8TF47-1
	ZFP90	NM_001305206.2		c.*120C>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.347C>T	p.Thr116Ile	missense	Exon 5 of 5	ENSP00000454418.2	Q8TF47-1
	ZFP90	ENST00000570495.5	TSL:1	c.347C>T	p.Thr116Ile	missense	Exon 5 of 5	ENSP00000460547.1	Q8TF47-1
	ZFP90	ENST00000611381.4	TSL:1	c.256+4566C>T		intron	N/A	ENSP00000480309.1	Q8TF47-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461838 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.4
DANN	Benign	0.81
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.00013	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.95	L
PhyloP100		-1.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.039
Sift	Benign	0.22	T
Sift4G	Benign	0.48	T
Polyphen		0.0020	B
Vest4		0.092
MutPred		0.28		Loss of disorder (P = 0.0166)
MVP		0.37
MPC		0.12
ClinPred		0.047	T
GERP RS		2.5
Varity_R		0.033
gMVP		0.32
Mutation Taster		=88/12	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: rs368733952; hg19: chr16-68597037;