rs766521550

Variant names:

• chr1-40457060-T-C
• rs766521550
• NM_023070.3:c.329T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-40457060-T-C
• chr1-40457060-T-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_023070.3(ZFP69B):​c.329T>C​(p.Leu110Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,202 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. L110R) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ZFP69B NM_023070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.67

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.958

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP69B	NM_023070.3	c.329T>C	p.Leu110Pro	missense_variant	Exon 3 of 5	ENST00000361584.5	NP_075558.2
ZFP69B	NM_001369565.1	c.329T>C	p.Leu110Pro	missense_variant	Exon 4 of 6		NP_001356494.1
ZFP69B	XM_005271136.2	c.329T>C	p.Leu110Pro	missense_variant	Exon 4 of 6		XP_005271193.1
ZFP69B	XM_017002147.2	c.329T>C	p.Leu110Pro	missense_variant	Exon 4 of 6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP69B	ENST00000361584.5	c.329T>C	p.Leu110Pro	missense_variant	Exon 3 of 5	1	NM_023070.3	ENSP00000354547.4
ZFP69B	ENST00000484445.5	c.243T>C	p.Pro81Pro	synonymous_variant	Exon 3 of 5	1		ENSP00000435907.1
ZFP69B	ENST00000411995.6	c.329T>C	p.Leu110Pro	missense_variant	Exon 4 of 6	5		ENSP00000399664.2
ZFP69B	ENST00000469416.1	n.709T>C		non_coding_transcript_exon_variant	Exon 4 of 5	2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;T
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.32	.;T
M_CAP	Benign	0.0089	T
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Pathogenic	4.5	H;H
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.1	D;.
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.91
MutPred		0.87		Loss of stability (P = 0.0567);Loss of stability (P = 0.0567);
MVP		0.24
MPC		0.62
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.90
gMVP		0.46

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: rs766521550; hg19: chr1-40922732;