chr5-180849489-C-T

Variant names:

• chr5-180849489-C-T
• NM_001172638.2:c.2006G>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001172638.2(ZFP62):​c.2006G>A​(p.Gly669Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZFP62 NM_001172638.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.78

Genes affected

ZFP62 (HGNC:23241): (ZFP62 zinc finger protein) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3917947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP62	NM_001172638.2	c.2006G>A	p.Gly669Glu	missense_variant	Exon 2 of 2	ENST00000502412.2	NP_001166109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZFP62	ENST00000502412.2	c.2006G>A	p.Gly669Glu	missense_variant	Exon 2 of 2	2	NM_001172638.2	ENSP00000423820.1
ZFP62	ENST00000506377.5	n.254-1407G>A		intron_variant	Intron 3 of 3	1
ZFP62	ENST00000512132.5	c.1907G>A	p.Gly636Glu	missense_variant	Exon 3 of 3	2		ENSP00000426193.1
ZFP62	ENST00000507843.1	n.28G>A		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 20, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2006G>A (p.G669E) alteration is located in exon 2 (coding exon 2) of the ZFP62 gene. This alteration results from a G to A substitution at nucleotide position 2006, causing the glycine (G) at amino acid position 669 to be replaced by a glutamic acid (E). 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	Pathogenic	0.89
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.3	.;L
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.5	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.020	D;.
Polyphen		1.0	.;D
Vest4		0.45
MutPred		0.45		.;Gain of solvent accessibility (P = 0.024);
MVP		0.57
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.61
gMVP		0.10

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: chr5-180276489; COSMIC: COSV63092367; COSMIC: COSV63092367;