Genetic Variant NM_001370215.1:c.399C>G (chr19-56621506-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001370215.1(ZNF71):c.399C>G(p.Pro133Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,614,096 control chromosomes in the GnomAD database, including 416 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. Synonymous variant affecting the same amino acid position (i.e. P133P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.031 ( 190 hom., cov: 33)

Exomes 𝑓: 0.0083 ( 226 hom. )

Consequence

ZNF71
NM_001370215.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.89

Publications

0 publications found

Variant links:

Genes affected

ZNF71 (HGNC:13141): (zinc finger protein 71) 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]

ZNF71 links:

ENSG00000293626 (HGNC:):

ENSG00000293626 links:

ZIM2-AS1 (HGNC:51304): (ZIM2 antisense RNA 1)

ZIM2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP7

Synonymous conserved (PhyloP=-2.89 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF71	NM_001370215.1 link	c.399C>G	p.Pro133Pro	synonymous_variant	Exon 4 of 4	ENST00000599599.7	NP_001357144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF71	ENST00000599599.7 link	c.399C>G	p.Pro133Pro	synonymous_variant	Exon 4 of 4	2	NM_001370215.1	ENSP00000471138.2		M0R0C0
ENSG00000293626	ENST00000716550.1 link	n.160+7568C>G		intron_variant	Intron 3 of 5			ENSP00000520562.1

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4687

AN:

152116

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0122

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00651

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.0111

AC:

2790

AN:

251050

AF XY:

0.00951

show subpopulations

Gnomad AFR exome

AF:

0.0962

Gnomad AMR exome

AF:

0.00668

Gnomad ASJ exome

AF:

0.0146

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00652

Gnomad OTH exome

AF:

0.00913

GnomAD4 exome

AF:

0.00828

AC:

12099

AN:

1461862

Hom.:

226

Cov.:

AF XY:

0.00793

AC XY:

5769

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0995

AC:

3329

AN:

33474

American (AMR)

AF:

0.00767

AC:

343

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0155

AC:

405

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39692

South Asian (SAS)

AF:

0.00173

AC:

149

AN:

86256

European-Finnish (FIN)

AF:

0.000637

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.0113

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00629

AC:

6996

AN:

1112006

Other (OTH)

AF:

0.0128

AC:

776

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

817

1634

2451

3268

4085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0309

AC:

4709

AN:

152234

Hom.:

190

Cov.:

AF XY:

0.0293

AC XY:

2180

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0955

AC:

3965

AN:

41522

American (AMR)

AF:

0.0122

AC:

187

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00124

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00651

AC:

443

AN:

68018

Other (OTH)

AF:

0.0194

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

212

424

635

847

1059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00572

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.36

(source)

DANN

Benign

0.46

PhyloP100

-2.9

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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NM_001370215.1:c.399C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over