Genetic Variant NM_001172638.2:c.2320G>T (chr5-180849175-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001172638.2(ZFP62):c.2320G>T(p.Val774Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZFP62
NM_001172638.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.454

Publications

0 publications found

Variant links:

Genes affected

ZFP62 (HGNC:23241): (ZFP62 zinc finger protein) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFP62 links:

HEIH (HGNC:45049): (hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA)

HEIH links:

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ACMG classification

Classification was made for transcript

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=0.08595249).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172638.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP62	NM_001172638.2	MANE Select	c.2320G>T	p.Val774Leu	missense	Exon 2 of 2	NP_001166109.1	Q8NB50-1
ZFP62	NM_001377943.1		c.2320G>T	p.Val774Leu	missense	Exon 2 of 2	NP_001364872.1	Q8NB50-1
ZFP62	NM_001377939.1		c.2221G>T	p.Val741Leu	missense	Exon 4 of 4	NP_001364868.1	Q8NB50-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZFP62	ENST00000502412.2	TSL:2 MANE Select	c.2320G>T	p.Val774Leu	missense	Exon 2 of 2	ENSP00000423820.1	Q8NB50-1
ZFP62	ENST00000506377.5	TSL:1	n.254-1093G>T		intron	N/A
ZFP62	ENST00000512132.5	TSL:2	c.2221G>T	p.Val741Leu	missense	Exon 3 of 3	ENSP00000426193.1	Q8NB50-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1410510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696640

African (AFR)

AF:

0.00

AC:

AN:

31858

American (AMR)

AF:

0.00

AC:

AN:

36704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25326

East Asian (EAS)

AF:

0.00

AC:

AN:

36484

South Asian (SAS)

AF:

0.00

AC:

AN:

79880

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50174

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085716

Other (OTH)

AF:

0.00

AC:

AN:

58656

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0030

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.21

M_CAP

Benign

0.0087

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.045

PhyloP100

-0.45

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.40

REVEL

Benign

0.068

Sift

Benign

0.35

Sift4G

Benign

0.34

Polyphen

0.010

Vest4

0.23

MutPred

0.23

Loss of MoRF binding (P = 0.0933)

MVP

0.13

ClinPred

0.13

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

gMVP

0.087

Mutation Taster

=97/3

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over