19-20624355-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001076675.3(ZNF626):c.1522T>C(p.Ser508Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (0 hom., cov: 27)
  • Exomes 𝑓: 0.0016 (52 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF626 NM_001076675.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.472

Genes affected

ZNF626 (HGNC:30461): (zinc finger protein 626) Predicted to enable DNA-binding transcription factor 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, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018360227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF626	NM_001076675.3	c.1522T>C	p.Ser508Pro	missense_variant	4/4	ENST00000601440.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF626	ENST00000601440.6	c.1522T>C	p.Ser508Pro	missense_variant	4/4	4	NM_001076675.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 286 AN: 77166 Hom.: 0 Cov.: 27 FAILED QC

Gnomad AFR AF: 0.00238

Gnomad AMI AF: 0.00765

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.00171

Gnomad EAS AF: 0.00711

Gnomad SAS AF: 0.00595

Gnomad FIN AF: 0.00728

Gnomad MID AF: 0.0278

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.00440

GnomAD3 exomes AF: 0.000916 AC: 218 AN: 237888 Hom.: 0 AF XY: 0.000910 AC XY: 118 AN XY: 129682

Gnomad AFR exome AF: 0.000868

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00157

Gnomad EAS exome AF: 0.00195

Gnomad SAS exome AF: 0.000946

Gnomad FIN exome AF: 0.000150

Gnomad NFE exome AF: 0.000764

Gnomad OTH exome AF: 0.00105

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00162 AC: 2128 AN: 1314070 Hom.: 52 Cov.: 33 AF XY: 0.00176 AC XY: 1138 AN XY: 647408

Gnomad4 AFR exome AF: 0.000960

Gnomad4 AMR exome AF: 0.00314

Gnomad4 ASJ exome AF: 0.00264

Gnomad4 EAS exome AF: 0.00381

Gnomad4 SAS exome AF: 0.00433

Gnomad4 FIN exome AF: 0.00186

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00197

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00370 AC: 286 AN: 77288 Hom.: 0 Cov.: 27 AF XY: 0.00359 AC XY: 134 AN XY: 37298

Gnomad4 AFR AF: 0.00237

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.00171

Gnomad4 EAS AF: 0.00753

Gnomad4 SAS AF: 0.00546

Gnomad4 FIN AF: 0.00728

Gnomad4 NFE AF: 0.00381

Gnomad4 OTH AF: 0.00431

Alfa AF: 0.00641 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.1522T>C (p.S508P) alteration is located in exon 4 (coding exon 4) of the ZNF626 gene. This alteration results from a T to C substitution at nucleotide position 1522, causing the serine (S) at amino acid position 508 to be replaced by a proline (P). 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	0.083
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	1.0
Dann	Benign	0.14
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0023	N
LIST_S2	Benign	0.0065	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.018	T
MutationTaster	Benign	1.0	N
Sift4G	Uncertain	0.040	D
Vest4		0.11
MVP		0.17
ClinPred		0.00056	T
GERP RS		-1.7

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

LitVar

Other links and lift over

dbSNP: rs1242995090; hg19: chr19-20807161; COSMIC: COSV105383121; COSMIC: COSV105383121;