Genetic Variant NM_152437.3:c.-757+6269G>T (chr12-123980289-G-T) – 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.-757+6269G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 151,982 control chromosomes in the GnomAD database, including 8,114 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 0.32 ( 8114 hom., cov: 32)

Consequence

ZNF664
NM_152437.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.230

Publications

26 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:

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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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ZNF664	NM_152437.3 link	c.-757+6269G>T	intron_variant	Intron 2 of 4	ENST00000337815.9	NP_689650.1	Q8N3J9A0A024RBR7
ZNF664	NM_001204298.2 link	c.-754+6269G>T	intron_variant	Intron 2 of 4		NP_001191227.1	Q8N3J9A0A024RBR7
ZNF664-RFLNA	NM_001204299.3 link	c.-234+6269G>T	intron_variant	Intron 2 of 4		NP_001191228.1	Q6ZTI6-2
ZNF664-RFLNA	NM_001347902.2 link	c.-234+6269G>T	intron_variant	Intron 2 of 4		NP_001334831.1	Q6ZTI6-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF664	ENST00000337815.9 link	c.-757+6269G>T		intron_variant	Intron 2 of 4	1	NM_152437.3	ENSP00000337320.4		Q8N3J9

Frequencies

GnomAD3 genomes

AF:

0.323

AC:

49073

AN:

151864

Hom.:

8108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.357

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.0934

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.337

Gnomad OTH

AF:

0.339

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

GnomAD4 genome

AF:

0.323

AC:

49113

AN:

151982

Hom.:

8114

Cov.:

AF XY:

0.315

AC XY:

23428

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.357

AC:

14796

AN:

41452

American (AMR)

AF:

0.296

AC:

4524

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

1354

AN:

3472

East Asian (EAS)

AF:

0.0934

AC:

484

AN:

5180

South Asian (SAS)

AF:

0.216

AC:

1041

AN:

4816

European-Finnish (FIN)

AF:

0.272

AC:

2866

AN:

10534

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.337

AC:

22894

AN:

67938

Other (OTH)

AF:

0.336

AC:

708

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1694

3388

5081

6775

8469

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.327

Hom.:

1730

Bravo

AF:

0.329

Asia WGS

AF:

0.212

AC:

737

AN:

3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.2

(source)

DANN

Benign

0.53

PhyloP100

0.23

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over