rs769989618

Variant names:

• chr1-40481838-C-A
• NM_001320179.2:c.203C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-40481838-C-A
• chr1-40481838-C-T

Variant summary

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

The NM_001320179.2(ZFP69):​c.203C>A​(p.Pro68Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,010 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. 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. P68L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZFP69 NM_001320179.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

Genes affected

ZFP69 (HGNC:24708): (ZFP69 zinc finger protein) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II and regulation of lipid metabolic process. Predicted to be located in nucleus. [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=0.056581795).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP69	NM_001320179.2	c.203C>A	p.Pro68Gln	missense_variant	Exon 3 of 6	ENST00000372706.6	NP_001307108.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP69	ENST00000372706.6	c.203C>A	p.Pro68Gln	missense_variant	Exon 3 of 6	1	NM_001320179.2	ENSP00000361791.1
ZFP69	ENST00000372705.3	c.203C>A	p.Pro68Gln	missense_variant	Exon 3 of 6	2		ENSP00000361790.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460010 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726464

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

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	0.081
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.047
DANN	Benign	0.50
DEOGEN2	Benign	0.020	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.036	.;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.012
Sift	Benign	0.36	T;T
Sift4G	Benign	0.090	T;T
Polyphen		0.0040	B;B
Vest4		0.16
MutPred		0.18		Loss of glycosylation at T69 (P = 0.0466);Loss of glycosylation at T69 (P = 0.0466);
MVP		0.061
MPC		0.16
ClinPred		0.046	T
GERP RS		-7.1
Varity_R		0.025
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: chr1-40947510;