rs1242995090

Variant names:

• chr19-20624355-A-G
• rs1242995090
• NM_001076675.3:c.1522T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-20624355-A-G
• chr19-20624355-A-C
• chr19-20624355-A-T

Variant summary

Our verdict is Likely benign. The variant received -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. 12/15 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
• Publications: 0 publications found

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]

ENSG00000269110 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001076675.3. 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
	ZNF626	NM_001076675.3	MANE Select	c.1522T>C	p.Ser508Pro	missense	Exon 4 of 4	NP_001070143.1	Q68DY1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF626	ENST00000601440.6	TSL:4 MANE Select	c.1522T>C	p.Ser508Pro	missense	Exon 4 of 4	ENSP00000469958.1	Q68DY1-1
	ENSG00000269110	ENST00000595094.1	TSL:5	n.363+21329T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00371 AC: 286 AN: 77166 Hom.: 0 Cov.: 27

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

GnomAD2 exomes AF: 0.000916 AC: 218 AN: 237888 AF XY: 0.000910

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 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

African (AFR) AF: 0.000960 AC: 30 AN: 31244

American (AMR) AF: 0.00314 AC: 117 AN: 37216

Ashkenazi Jewish (ASJ) AF: 0.00264 AC: 59 AN: 22364

East Asian (EAS) AF: 0.00381 AC: 118 AN: 30972

South Asian (SAS) AF: 0.00433 AC: 317 AN: 73130

European-Finnish (FIN) AF: 0.00186 AC: 83 AN: 44670

Middle Eastern (MID) AF: 0.00166 AC: 7 AN: 4208

European-Non Finnish (NFE) AF: 0.00127 AC: 1294 AN: 1017976

Other (OTH) AF: 0.00197 AC: 103 AN: 52290

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00237 AC: 63 AN: 26562

American (AMR) AF: 0.00412 AC: 24 AN: 5830

Ashkenazi Jewish (ASJ) AF: 0.00171 AC: 3 AN: 1758

East Asian (EAS) AF: 0.00753 AC: 18 AN: 2392

South Asian (SAS) AF: 0.00546 AC: 11 AN: 2016

European-Finnish (FIN) AF: 0.00728 AC: 31 AN: 4258

Middle Eastern (MID) AF: 0.0294 AC: 3 AN: 102

European-Non Finnish (NFE) AF: 0.00381 AC: 126 AN: 33050

Other (OTH) AF: 0.00431 AC: 4 AN: 928

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00641 Hom.: 0

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	0.083
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
PhyloP100		0.47
Sift4G	Uncertain	0.040	D
Vest4		0.11
MVP		0.17
ClinPred		0.00056	T
GERP RS		-1.7
Varity_R		0.038
Mutation Taster		=99/1	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

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