1-40462678-A-G

Variant names:

• chr1-40462678-A-G
• NM_023070.3:c.694A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023070.3(ZFP69B):​c.694A>G​(p.Ile232Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZFP69B NM_023070.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.414

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_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053547233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP69B	NM_023070.3	c.694A>G	p.Ile232Val	missense_variant	Exon 5 of 5	ENST00000361584.5	NP_075558.2
ZFP69B	NM_001369565.1	c.694A>G	p.Ile232Val	missense_variant	Exon 6 of 6		NP_001356494.1
ZFP69B	XM_005271136.2	c.697A>G	p.Ile233Val	missense_variant	Exon 6 of 6		XP_005271193.1
ZFP69B	XM_017002147.2	c.697A>G	p.Ile233Val	missense_variant	Exon 6 of 6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP69B	ENST00000361584.5	c.694A>G	p.Ile232Val	missense_variant	Exon 5 of 5	1	NM_023070.3	ENSP00000354547.4
ZFP69B	ENST00000484445.5	c.*212A>G		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000435907.1
ZFP69B	ENST00000411995.6	c.694A>G	p.Ile232Val	missense_variant	Exon 6 of 6	5		ENSP00000399664.2
ZFP69B	ENST00000469416.1	n.1346A>G		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.694A>G (p.I232V) alteration is located in exon 5 (coding exon 5) of the ZFP69B gene. This alteration results from a A to G substitution at nucleotide position 694, causing the isoleucine (I) at amino acid position 232 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.2
DANN	Benign	0.79
DEOGEN2	Benign	0.0013	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.000020	N
LIST_S2	Benign	0.15	.;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.054	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.76	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.53	N;.
REVEL	Benign	0.030
Sift	Benign	0.47	T;.
Sift4G	Benign	0.46	T;T
Polyphen		0.0010	B;B
Vest4		0.11
MutPred		0.46		Loss of stability (P = 0.0901);Loss of stability (P = 0.0901);
MVP		0.085
MPC		0.079
ClinPred		0.041	T
GERP RS		0.58
Varity_R		0.038
gMVP		0.026

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40928350;