Genetic Variant ZNF664:c.-660-4399G>C (chr12-124006982-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152437.3(ZNF664):c.-660-4399G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,000 control chromosomes in the GnomAD database, including 29,566 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.61 ( 29566 hom., cov: 31)

Consequence

ZNF664
NM_152437.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.264

Publications

25 publications found

Variant links:

Genes affected

ZNF664 (HGNC:25406): (zinc finger protein 664) Predicted to enable DNA-binding transcription factor 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, DNA-templated. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF664 links:

ZNF664-RFLNA (HGNC:):

ZNF664-RFLNA links:

RFLNA (HGNC:27051): (refilin A) Predicted to enable filamin binding activity. Predicted to be involved in several processes, including actin filament bundle organization; negative regulation of bone mineralization involved in bone maturation; and negative regulation of chondrocyte development. Predicted to be located in cytoplasm. Predicted to be active in actin filament bundle. [provided by Alliance of Genome Resources, Apr 2022]

RFLNA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF664	NM_152437.3	MANE Select	c.-660-4399G>C	intron	N/A	NP_689650.1	Q8N3J9
ZNF664	NM_001204298.2		c.-660-4399G>C	intron	N/A	NP_001191227.1	Q8N3J9
ZNF664-RFLNA	NM_001204299.3		c.-234+32962G>C	intron	N/A	NP_001191228.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ZNF664	ENST00000337815.9	TSL:1 MANE Select	c.-660-4399G>C	intron	N/A	ENSP00000337320.4	Q8N3J9
ZNF664	ENST00000392404.7	TSL:1	c.-660-4399G>C	intron	N/A	ENSP00000376205.3	Q8N3J9
ZNF664	ENST00000539644.5	TSL:1	c.-661+2047G>C	intron	N/A	ENSP00000441405.1	Q8N3J9

Frequencies

GnomAD3 genomes

AF:

0.611

AC:

92839

AN:

151882

Hom.:

29560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.626

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.564

Gnomad EAS

AF:

0.907

Gnomad SAS

AF:

0.783

Gnomad FIN

AF:

0.719

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.601

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.611

AC:

92882

AN:

152000

Hom.:

29566

Cov.:

AF XY:

0.621

AC XY:

46129

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.431

AC:

17862

AN:

41448

American (AMR)

AF:

0.672

AC:

10254

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

1954

AN:

3466

East Asian (EAS)

AF:

0.907

AC:

4683

AN:

5164

South Asian (SAS)

AF:

0.784

AC:

3779

AN:

4822

European-Finnish (FIN)

AF:

0.719

AC:

7592

AN:

10558

Middle Eastern (MID)

AF:

0.551

AC:

162

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44754

AN:

67962

Other (OTH)

AF:

0.604

AC:

1271

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1740

3480

5220

6960

8700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.628

Hom.:

3654

Bravo

AF:

0.595

Asia WGS

AF:

0.768

AC:

2672

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.49

(source)

DANN

Benign

0.50

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over