NM_001305203.2:c.617C>T

Variant names:

• chr16-68563404-C-T
• rs371755481
• NM_001305203.2:c.617C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001305203.2(ZFP90):​c.617C>T​(p.Ala206Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,610,146 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZFP90 NM_001305203.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.824
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07184386).

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.617C>T	p.Ala206Val	missense	Exon 5 of 5	NP_001292132.1	Q8TF47-1
	ZFP90	NM_133458.4		c.617C>T	p.Ala206Val	missense	Exon 5 of 5	NP_597715.2	Q8TF47-1
	ZFP90	NM_001305206.2		c.*390C>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.617C>T	p.Ala206Val	missense	Exon 5 of 5	ENSP00000454418.2	Q8TF47-1
	ZFP90	ENST00000570495.5	TSL:1	c.617C>T	p.Ala206Val	missense	Exon 5 of 5	ENSP00000460547.1	Q8TF47-1
	ZFP90	ENST00000611381.4	TSL:1	c.256+4836C>T		intron	N/A	ENSP00000480309.1	Q8TF47-3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151934 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: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000410 AC: 1 AN: 244084 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000900

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458212 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725260

African (AFR) AF: 0.00 AC: 0 AN: 33114

American (AMR) AF: 0.00 AC: 0 AN: 43780

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 85296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111150

Other (OTH) AF: 0.00 AC: 0 AN: 60204

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151934 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74202

African (AFR) AF: 0.00 AC: 0 AN: 41368

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10524

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67980

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000251 Hom.: 0

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000123 AC: 1

ExAC AF: 0.00000828 AC: 1

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	Benign	0.14
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.6
DANN	Benign	0.94
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.00019	N
LIST_S2	Benign	0.055	T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L
PhyloP100		0.82
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.043
Sift	Benign	0.096	T
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.033
MVP		0.28
MPC		0.11
ClinPred		0.074	T
GERP RS		1.0
Varity_R		0.021
gMVP		0.11

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: rs371755481; hg19: chr16-68597307;