rs78797427

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-57720878-C-T
• chr19-57720878-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024833.3(ZNF671):​c.1208G>A​(p.Gly403Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,614,124 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (49 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (50 hom.)
• Consequence: ZNF671 NM_024833.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040881634).
• BP6: Variant 19-57720878-C-T is Benign according to our data. Variant chr19-57720878-C-T is described in ClinVar as Benign. ClinVar VariationId is 769060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2140/152230) while in subpopulation AFR AF = 0.0492 (2041/41520). AF 95% confidence interval is 0.0474. There are 49 homozygotes in GnomAd4. There are 976 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 49 AR gene

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>A	p.Gly403Glu	missense	Exon 4 of 4	NP_079109.2	Q8TAW3
	ZNF671	NM_001321376.2		c.977G>A	p.Gly326Glu	missense	Exon 5 of 5	NP_001308305.1
	ZNF671	NM_001321375.2		c.914G>A	p.Gly305Glu	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>A	p.Gly403Glu	missense	Exon 4 of 4	ENSP00000321848.5	Q8TAW3
	ENSG00000269026	ENST00000594684.1	TSL:1	c.34-29907C>T		intron	N/A	ENSP00000472160.1	M0R1X1
	ZNF671	ENST00000925804.1		c.1370G>A	p.Gly457Glu	missense	Exon 4 of 4	ENSP00000595864.1

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2132 AN: 152112 Hom.: 49 Cov.: 33

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0105

GnomAD2 exomes AF: 0.00345 AC: 867 AN: 251476 AF XY: 0.00254

Gnomad AFR exome AF: 0.0477

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000193

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00145 AC: 2117 AN: 1461894 Hom.: 50 Cov.: 35 AF XY: 0.00120 AC XY: 870 AN XY: 727248

African (AFR) AF: 0.0494 AC: 1655 AN: 33480

American (AMR) AF: 0.00235 AC: 105 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00381 AC: 22 AN: 5768

European-Non Finnish (NFE) AF: 0.0000980 AC: 109 AN: 1112012

Other (OTH) AF: 0.00361 AC: 218 AN: 60396

GnomAD4 genome AF: 0.0141 AC: 2140 AN: 152230 Hom.: 49 Cov.: 33 AF XY: 0.0131 AC XY: 976 AN XY: 74420

African (AFR) AF: 0.0492 AC: 2041 AN: 41520

American (AMR) AF: 0.00432 AC: 66 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68020

Other (OTH) AF: 0.0104 AC: 22 AN: 2112

Alfa AF: 0.00500 Hom.: 35

Bravo AF: 0.0165

ESP6500AA AF: 0.0486 AC: 214

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00437 AC: 531

Asia WGS AF: 0.00346 AC: 12 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.77
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.065
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.13
MVP		0.58
MPC		0.75
ClinPred		0.075	T
GERP RS		0.81
Varity_R		0.58
gMVP		0.084
Mutation Taster		=97/3	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; COSMIC: COSV58052066; COSMIC: COSV58052066;