chr19-57720878-C-G

Variant names:

• chr19-57720878-C-G
• rs78797427
• NM_024833.3:c.1208G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024833.3(ZNF671):​c.1208G>C​(p.Gly403Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. G403E) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF671 NM_024833.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769
• Publications: 5 publications found

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]

ENSG00000269026 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38081664).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF671	NM_024833.3	MANE Select	c.1208G>C	p.Gly403Ala	missense	Exon 4 of 4	NP_079109.2	Q8TAW3
	ZNF671	NM_001321376.2		c.977G>C	p.Gly326Ala	missense	Exon 5 of 5	NP_001308305.1
	ZNF671	NM_001321375.2		c.914G>C	p.Gly305Ala	missense	Exon 3 of 3	NP_001308304.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF671	ENST00000317398.10	TSL:1 MANE Select	c.1208G>C	p.Gly403Ala	missense	Exon 4 of 4	ENSP00000321848.5	Q8TAW3
	ENSG00000269026	ENST00000594684.1	TSL:1	c.34-29907C>G		intron	N/A	ENSP00000472160.1	M0R1X1
	ZNF671	ENST00000925804.1		c.1370G>C	p.Gly457Ala	missense	Exon 4 of 4	ENSP00000595864.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.090
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.77
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.036
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.69		Loss of ubiquitination at K404 (P = 0.0896)
MVP		0.55
MPC		0.68
ClinPred		0.97	D
GERP RS		0.81
Varity_R		0.47
gMVP		0.082
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs78797427; hg19: chr19-58232246;