1-40457030-G-T

Variant names:

• chr1-40457030-G-T
• NM_023070.3:c.299G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_023070.3(ZFP69B):​c.299G>T​(p.Arg100Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R100Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZFP69B NM_023070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP69B	NM_023070.3	c.299G>T	p.Arg100Leu	missense_variant	Exon 3 of 5	ENST00000361584.5	NP_075558.2
ZFP69B	NM_001369565.1	c.299G>T	p.Arg100Leu	missense_variant	Exon 4 of 6		NP_001356494.1
ZFP69B	XM_005271136.2	c.299G>T	p.Arg100Leu	missense_variant	Exon 4 of 6		XP_005271193.1
ZFP69B	XM_017002147.2	c.299G>T	p.Arg100Leu	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.299G>T	p.Arg100Leu	missense_variant	Exon 3 of 5	1	NM_023070.3	ENSP00000354547.4
ZFP69B	ENST00000484445.5	c.213G>T	p.Pro71Pro	synonymous_variant	Exon 3 of 5	1		ENSP00000435907.1
ZFP69B	ENST00000411995.6	c.299G>T	p.Arg100Leu	missense_variant	Exon 4 of 6	5		ENSP00000399664.2
ZFP69B	ENST00000469416.1	n.679G>T		non_coding_transcript_exon_variant	Exon 4 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459678 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726122

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	0.0060	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	0.023
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.12	.;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M;M
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.0	D;.
REVEL	Benign	0.23
Sift	Uncertain	0.024	D;.
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.14	B;B
Vest4		0.71
MutPred		0.68		Gain of catalytic residue at E101 (P = 0.1275);Gain of catalytic residue at E101 (P = 0.1275);
MVP		0.16
MPC		0.54
ClinPred		0.94	D
GERP RS		3.3
Varity_R		0.52
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40922702;