1-40454236-G-A

Position:

• chr1-40454236-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_023070.3(ZFP69B):​c.161G>A​(p.Gly54Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZFP69B NM_023070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.626

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=0.074496746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFP69B	NM_023070.3	c.161G>A	p.Gly54Asp	missense_variant	2/5	ENST00000361584.5
ZFP69B	NM_001369565.1	c.161G>A	p.Gly54Asp	missense_variant	3/6
ZFP69B	XM_005271136.2	c.161G>A	p.Gly54Asp	missense_variant	3/6
ZFP69B	XM_017002147.2	c.161G>A	p.Gly54Asp	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFP69B	ENST00000361584.5	c.161G>A	p.Gly54Asp	missense_variant	2/5	1	NM_023070.3	P1
ZFP69B	ENST00000484445.5	c.128-2709G>A		intron_variant		1
ZFP69B	ENST00000411995.6	c.161G>A	p.Gly54Asp	missense_variant	3/6	5		P1
ZFP69B	ENST00000469416.1	n.541G>A		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244520 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 132996

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1453416 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 722744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000226

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.9
DANN	Benign	0.83
DEOGEN2	Benign	0.00090	T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.017	N
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.038
Sift	Benign	0.13	T;.
Sift4G	Benign	0.52	T;T
Polyphen		0.67	P;P
Vest4		0.28
MutPred		0.27		Gain of solvent accessibility (P = 0.0281);Gain of solvent accessibility (P = 0.0281);
MVP		0.072
MPC		0.26
ClinPred		0.073	T
GERP RS		0.82
Varity_R		0.057
gMVP		0.15

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: rs1376866807; hg19: chr1-40919908;