dbSNP rs773804519: ZFP69B:p.Ile162Thr (chr1-40462469-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023070.3(ZFP69B):c.485T>C(p.Ile162Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. I162S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ZFP69B
NM_023070.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0360

Variant links:

Genes affected

ZFP69B (HGNC:28053): (ZFP69 zinc finger protein B) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in Golgi organization. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ZFP69B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10330215).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP69B	NM_023070.3 link	c.485T>C	p.Ile162Thr	missense_variant	Exon 5 of 5	ENST00000361584.5	NP_075558.2	Q9UJL9-1
ZFP69B	NM_001369565.1 link	c.485T>C	p.Ile162Thr	missense_variant	Exon 6 of 6		NP_001356494.1
ZFP69B	XM_005271136.2 link	c.488T>C	p.Ile163Thr	missense_variant	Exon 6 of 6		XP_005271193.1
ZFP69B	XM_017002147.2 link	c.488T>C	p.Ile163Thr	missense_variant	Exon 6 of 6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZFP69B	ENST00000361584.5 link	c.485T>C	p.Ile162Thr	missense_variant	Exon 5 of 5	1	NM_023070.3	ENSP00000354547.4	Q9UJL9-1
ZFP69B	ENST00000484445.5 link	c.*3T>C		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000435907.1	E9PS66
ZFP69B	ENST00000411995.6 link	c.485T>C	p.Ile162Thr	missense_variant	Exon 6 of 6	5		ENSP00000399664.2	Q9UJL9-1
ZFP69B	ENST00000469416.1 link	n.1137T>C		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248034

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134030

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000889

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459248

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725752

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

8.6

DANN

Benign

0.81

DEOGEN2

Benign

0.025

T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.00010

LIST_S2

Benign

0.57

.;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.0

D;N

REVEL

Benign

0.036

Sift

Benign

0.097

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.55

P;P

Vest4

0.14

MutPred

0.45

Gain of disorder (P = 0.0202);Gain of disorder (P = 0.0202);

MVP

0.085

MPC

0.14

ClinPred

0.31

GERP RS

2.3

Varity_R

0.067

gMVP

0.069

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over