1-40457006-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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

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=0.2180863).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP69B	NM_023070.3	c.275C>T	p.Ala92Val	missense_variant	Exon 3 of 5	ENST00000361584.5	NP_075558.2
ZFP69B	NM_001369565.1	c.275C>T	p.Ala92Val	missense_variant	Exon 4 of 6		NP_001356494.1
ZFP69B	XM_005271136.2	c.275C>T	p.Ala92Val	missense_variant	Exon 4 of 6		XP_005271193.1
ZFP69B	XM_017002147.2	c.275C>T	p.Ala92Val	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.275C>T	p.Ala92Val	missense_variant	Exon 3 of 5	1	NM_023070.3	ENSP00000354547.4
ZFP69B	ENST00000484445.5	c.189C>T	p.Gly63Gly	synonymous_variant	Exon 3 of 5	1		ENSP00000435907.1
ZFP69B	ENST00000411995.6	c.275C>T	p.Ala92Val	missense_variant	Exon 4 of 6	5		ENSP00000399664.2
ZFP69B	ENST00000469416.1	n.655C>T		non_coding_transcript_exon_variant	Exon 4 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.85	L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.6	N;.
REVEL	Benign	0.077
Sift	Benign	0.071	T;.
Sift4G	Uncertain	0.027	D;D
Polyphen		0.67	P;P
Vest4		0.40
MutPred		0.60		Loss of disorder (P = 0.1956);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

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: rs976942564; hg19: chr1-40922678;