Genetic Variant ZNF671:p.Ser437Asn (chr19-57720776-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024833.3(ZNF671):c.1310G>A(p.Ser437Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. S437I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ZNF671
NM_024833.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.86

Publications

0 publications found

Variant links:

Genes affected

ZNF671 (HGNC:26279): (zinc finger protein 671) Predicted to enable DNA-binding transcription factor activity 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF671 links:

ENSG00000269026 (HGNC:):

ENSG00000269026 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.053195328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024833.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF671	NM_024833.3	MANE Select	c.1310G>A	p.Ser437Asn	missense	Exon 4 of 4	NP_079109.2	Q8TAW3
ZNF671	NM_001321376.2		c.1079G>A	p.Ser360Asn	missense	Exon 5 of 5	NP_001308305.1
ZNF671	NM_001321375.2		c.1016G>A	p.Ser339Asn	missense	Exon 3 of 3	NP_001308304.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF671	ENST00000317398.10	TSL:1 MANE Select	c.1310G>A	p.Ser437Asn	missense	Exon 4 of 4	ENSP00000321848.5	Q8TAW3
ENSG00000269026	ENST00000594684.1	TSL:1	c.34-30009C>T		intron	N/A	ENSP00000472160.1	M0R1X1
ZNF671	ENST00000925804.1		c.1472G>A	p.Ser491Asn	missense	Exon 4 of 4	ENSP00000595864.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.22

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.0096

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.27

M_CAP

Benign

0.0014

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.3

PhyloP100

-5.9

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.80

REVEL

Benign

0.024

Sift

Benign

0.33

Sift4G

Benign

0.24

Polyphen

0.0010

Vest4

0.044

MutPred

0.31

Loss of ubiquitination at K432 (P = 0.0777)

MVP

0.35

MPC

0.14

ClinPred

0.066

GERP RS

-2.4

Varity_R

0.063

gMVP

0.062

Mutation Taster

=99/1

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over