1-40451005-C-T

Variant names:

• chr1-40451005-C-T
• NM_023070.3:c.44C>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.44C>T​(p.Thr15Ile) 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. 12/21 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: 0.101

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=0.116993755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP69B	NM_023070.3	c.44C>T	p.Thr15Ile	missense_variant	Exon 1 of 5	ENST00000361584.5	NP_075558.2
ZFP69B	NM_001369565.1	c.44C>T	p.Thr15Ile	missense_variant	Exon 2 of 6		NP_001356494.1
ZFP69B	XM_005271136.2	c.44C>T	p.Thr15Ile	missense_variant	Exon 2 of 6		XP_005271193.1
ZFP69B	XM_017002147.2	c.44C>T	p.Thr15Ile	missense_variant	Exon 2 of 6		XP_016857636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP69B	ENST00000361584.5	c.44C>T	p.Thr15Ile	missense_variant	Exon 1 of 5	1	NM_023070.3	ENSP00000354547.4
ZFP69B	ENST00000484445.5	c.44C>T	p.Thr15Ile	missense_variant	Exon 2 of 5	1		ENSP00000435907.1
ZFP69B	ENST00000411995.6	c.44C>T	p.Thr15Ile	missense_variant	Exon 2 of 6	5		ENSP00000399664.2
ZFP69B	ENST00000469416.1	n.424C>T		non_coding_transcript_exon_variant	Exon 2 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.44C>T (p.T15I) alteration is located in exon 1 (coding exon 1) of the ZFP69B gene. This alteration results from a C to T substitution at nucleotide position 44, causing the threonine (T) at amino acid position 15 to be replaced by an isoleucine (I). 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	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0020	.;T;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.81	T;.;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	.;M;M
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.6	D;N;.
REVEL	Benign	0.011
Sift	Uncertain	0.0060	D;T;.
Sift4G	Uncertain	0.016	D;D;D
Polyphen		0.22	.;B;B
Vest4		0.32
MutPred		0.43		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.072
MPC		0.13
ClinPred		0.16	T
GERP RS		1.9
Varity_R		0.042
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-40916677;