Genetic Variant NM_024833.3:c.944G>C (chr19-57721142-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024833.3(ZNF671):c.944G>C(p.Cys315Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. C315Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF671
NM_024833.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.21

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: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.852

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.944G>C	p.Cys315Ser	missense	Exon 4 of 4	NP_079109.2	Q8TAW3
ZNF671	NM_001321376.2		c.713G>C	p.Cys238Ser	missense	Exon 5 of 5	NP_001308305.1
ZNF671	NM_001321375.2		c.650G>C	p.Cys217Ser	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.944G>C	p.Cys315Ser	missense	Exon 4 of 4	ENSP00000321848.5	Q8TAW3
ENSG00000269026	ENST00000594684.1	TSL:1	c.34-29643C>G		intron	N/A	ENSP00000472160.1	M0R1X1
ZNF671	ENST00000925804.1		c.1106G>C	p.Cys369Ser	missense	Exon 4 of 4	ENSP00000595864.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251444

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727228

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:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111994

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.40

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.057

M_CAP

Benign

0.032

MetaRNN

Pathogenic

0.85

MetaSVM

Uncertain

0.076

MutationAssessor

Pathogenic

4.0

PhyloP100

3.2

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-9.6

REVEL

Uncertain

0.37

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.34

MutPred

0.77

Gain of disorder (P = 0.0199)

MVP

0.87

MPC

0.73

ClinPred

1.0

GERP RS

1.9

Varity_R

0.70

gMVP

0.30

Mutation Taster

=86/14

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