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. Variant got 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. 13/16 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP69B	NM_023070.3	c.445A>C	p.Ser149Arg	missense_variant	Exon 5 of 5	ENST00000361584.5	NP_075558.2
ZFP69B	NM_001369565.1	c.445A>C	p.Ser149Arg	missense_variant	Exon 6 of 6		NP_001356494.1
ZFP69B	XM_005271136.2	c.448A>C	p.Ser150Arg	missense_variant	Exon 6 of 6		XP_005271193.1
ZFP69B	XM_017002147.2	c.448A>C	p.Ser150Arg	missense_variant	Exon 6 of 6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP69B	ENST00000361584.5	c.445A>C	p.Ser149Arg	missense_variant	Exon 5 of 5	1	NM_023070.3	ENSP00000354547.4
ZFP69B	ENST00000484445.5	c.359A>C	p.Glu120Ala	missense_variant	Exon 5 of 5	1		ENSP00000435907.1
ZFP69B	ENST00000411995.6	c.445A>C	p.Ser149Arg	missense_variant	Exon 6 of 6	5		ENSP00000399664.2
ZFP69B	ENST00000469416.1	n.1097A>C		non_coding_transcript_exon_variant	Exon 5 of 5	2

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

LitVar

Other links and lift over

dbSNP: rs773022185; hg19: chr1-40928101;