5-180849553-C-T

Variant names:

• chr5-180849553-C-T
• NM_001172638.2:c.1942G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001172638.2(ZFP62):​c.1942G>A​(p.Asp648Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ZFP62 NM_001172638.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0670
• Publications: 0 publications found

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]

HEIH (HGNC:45049): (hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05801046).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172638.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP62	NM_001172638.2	MANE Select	c.1942G>A	p.Asp648Asn	missense	Exon 2 of 2	NP_001166109.1	Q8NB50-1
	ZFP62	NM_001377943.1		c.1942G>A	p.Asp648Asn	missense	Exon 2 of 2	NP_001364872.1	Q8NB50-1
	ZFP62	NM_001377939.1		c.1843G>A	p.Asp615Asn	missense	Exon 4 of 4	NP_001364868.1	Q8NB50-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZFP62	ENST00000502412.2	TSL:2 MANE Select	c.1942G>A	p.Asp648Asn	missense	Exon 2 of 2	ENSP00000423820.1	Q8NB50-1
	ZFP62	ENST00000506377.5	TSL:1	n.254-1471G>A		intron	N/A
	ZFP62	ENST00000512132.5	TSL:2	c.1843G>A	p.Asp615Asn	missense	Exon 3 of 3	ENSP00000426193.1	Q8NB50-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399974 Hom.: 0 Cov.: 78 AF XY: 0.00000145 AC XY: 1 AN XY: 690454

African (AFR) AF: 0.00 AC: 0 AN: 31602

American (AMR) AF: 0.00 AC: 0 AN: 35706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35740

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079114

Other (OTH) AF: 0.00 AC: 0 AN: 58170

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.0016	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.067
PrimateAI	Benign	0.44	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.090
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.065	B
Vest4		0.19
MutPred		0.22		Loss of ubiquitination at K652 (P = 0.0331)
MVP		0.27
ClinPred		0.36	T
GERP RS		4.6
Varity_R		0.045
gMVP		0.061
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

hg19: chr5-180276553;