rs773022185

Variant names:

• chr1-40462429-A-C
• rs773022185
• NM_023070.3:c.445A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-40462429-A-C
• chr1-40462429-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023070.3(ZFP69B):​c.445A>C​(p.Ser149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,428,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 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. S149G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZFP69B NM_023070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676
• Publications: 0 publications found

Genes affected

ZFP69B (HGNC:28053): (ZFP69 zinc finger protein B) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in Golgi organization. Located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09095761).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023070.3. 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
	ZFP69B	NM_023070.3	MANE Select	c.445A>C	p.Ser149Arg	missense	Exon 5 of 5	NP_075558.2	Q9UJL9-1
	ZFP69B	NM_001369565.1		c.445A>C	p.Ser149Arg	missense	Exon 6 of 6	NP_001356494.1	Q9UJL9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP69B	ENST00000361584.5	TSL:1 MANE Select	c.445A>C	p.Ser149Arg	missense	Exon 5 of 5	ENSP00000354547.4	Q9UJL9-1
	ZFP69B	ENST00000484445.5	TSL:1	c.359A>C	p.Glu120Ala	missense	Exon 5 of 5	ENSP00000435907.1	E9PS66
	ZFP69B	ENST00000863980.1		c.448A>C	p.Ser150Arg	missense	Exon 6 of 6	ENSP00000534039.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000210 AC: 3 AN: 1428326 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 709294

African (AFR) AF: 0.00 AC: 0 AN: 31318

American (AMR) AF: 0.00 AC: 0 AN: 34936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24236

East Asian (EAS) AF: 0.00 AC: 0 AN: 39502

South Asian (SAS) AF: 0.00 AC: 0 AN: 80032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5604

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1101192

Other (OTH) AF: 0.00 AC: 0 AN: 58928

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.6
DANN	Benign	0.93
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.000040	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.68
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.051
Sift	Pathogenic	0.0	D
Vest4		0.21
MutPred		0.27		Loss of helix (P = 0.0123)
MVP		0.16
ClinPred		0.13	T
GERP RS		0.97
Varity_R		0.10
Mutation Taster		=99/1	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: rs773022185; hg19: chr1-40928101;