1-40457006-C-T

Variant names:

• chr1-40457006-C-T
• rs976942564
• NM_023070.3:c.275C>T

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.275C>T​(p.Ala92Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. A92D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP69B NM_023070.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• 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=0.2180863).

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.275C>T	p.Ala92Val	missense	Exon 3 of 5	NP_075558.2	Q9UJL9-1
	ZFP69B	NM_001369565.1		c.275C>T	p.Ala92Val	missense	Exon 4 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.275C>T	p.Ala92Val	missense	Exon 3 of 5	ENSP00000354547.4	Q9UJL9-1
	ZFP69B	ENST00000484445.5	TSL:1	c.189C>T	p.Gly63Gly	synonymous	Exon 3 of 5	ENSP00000435907.1	E9PS66
	ZFP69B	ENST00000863980.1		c.275C>T	p.Ala92Val	missense	Exon 4 of 6	ENSP00000534039.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.85	L
PhyloP100		0.086
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.077
Sift	Benign	0.071	T
Sift4G	Uncertain	0.027	D
Polyphen		0.67	P
Vest4		0.40
MutPred		0.60		Loss of disorder (P = 0.1956)
MVP		0.41
MPC		0.13
ClinPred		0.52	D
GERP RS		3.3
Varity_R		0.050
gMVP		0.051
Mutation Taster		=97/3	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: rs976942564; hg19: chr1-40922678;