dbSNP rs12310367: ZNF664:c.-660-9250A>G (chr12-124002131-A-G) – 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.-660-9250A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,118 control chromosomes in the GnomAD database, including 8,171 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 ( 8171 hom., cov: 32)

Consequence

ZNF664
NM_152437.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.328

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:

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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 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.-660-9250A>G	intron	N/A	NP_689650.1	Q8N3J9
ZNF664	NM_001204298.2		c.-660-9250A>G	intron	N/A	NP_001191227.1	Q8N3J9
ZNF664-RFLNA	NM_001204299.3		c.-234+28111A>G	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.-660-9250A>G	intron	N/A	ENSP00000337320.4	Q8N3J9
ZNF664	ENST00000392404.7	TSL:1	c.-660-9250A>G	intron	N/A	ENSP00000376205.3	Q8N3J9
ZNF664	ENST00000539644.5	TSL:1	c.-836-1292A>G	intron	N/A	ENSP00000441405.1	Q8N3J9

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49226

AN:

152000

Hom.:

8165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.358

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.0934

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.354

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:

0.324

AC:

49266

AN:

152118

Hom.:

8171

Cov.:

AF XY:

0.316

AC XY:

23514

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.358

AC:

14848

AN:

41476

American (AMR)

AF:

0.295

AC:

4507

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.419

AC:

1456

AN:

3472

East Asian (EAS)

AF:

0.0933

AC:

483

AN:

5178

South Asian (SAS)

AF:

0.215

AC:

1034

AN:

4818

European-Finnish (FIN)

AF:

0.271

AC:

2866

AN:

10582

Middle Eastern (MID)

AF:

0.366

AC:

107

AN:

292

European-Non Finnish (NFE)

AF:

0.337

AC:

22920

AN:

67982

Other (OTH)

AF:

0.336

AC:

708

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1681

3363

5044

6726

8407

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:

0.333

Hom.:

11556

Bravo

AF:

0.330

Asia WGS

AF:

0.214

AC:

744

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

3.4

(source)

DANN

Benign

0.58

PhyloP100

0.33

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