chr5-180849585-C-T

Variant names:

• chr5-180849585-C-T
• NM_001172638.2:c.1910G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001172638.2(ZFP62):​c.1910G>A​(p.Arg637Lys) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R637S) has been classified 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: 0.283

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22070703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZFP62	NM_001172638.2	c.1910G>A	p.Arg637Lys	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.1910G>A	p.Arg637Lys	missense_variant	Exon 2 of 2	2	NM_001172638.2	ENSP00000423820.1
ZFP62	ENST00000506377.5	n.254-1503G>A		intron_variant	Intron 3 of 3	1
ZFP62	ENST00000512132.5	c.1811G>A	p.Arg604Lys	missense_variant	Exon 3 of 3	2		ENSP00000426193.1
ZFP62	ENST00000507843.1	n.-69G>A		upstream_gene_variant		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 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1910G>A (p.R637K) 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 1910, causing the arginine (R) at amino acid position 637 to be replaced by a lysine (K). 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	Uncertain	0.37
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0099	.;T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.27	T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	.;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.15
Sift	Benign	0.12	T;T
Sift4G	Benign	0.16	T;.
Polyphen		1.0	.;D
Vest4		0.14
MutPred		0.60		.;Gain of methylation at R637 (P = 0.0071);
MVP		0.58
ClinPred		0.58	D
GERP RS		4.6
Varity_R		0.18
gMVP		0.20

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: chr5-180276585;