chr12-132922352-G-A

Variant names:

• chr12-132922352-G-A
• rs1278602
• NM_183238.4:c.*3021C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183238.4(ZNF605):​c.*3021C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,034 control chromosomes in the GnomAD database, including 13,965 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (13965 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ZNF605 NM_183238.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.559
• Publications: 11 publications found

Genes affected

ZNF605 (HGNC:28068): (zinc finger protein 605) 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 by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CHFR (HGNC:20455): (checkpoint with forkhead and ring finger domains) This gene encodes an E3 ubiquitin-protein ligase required for the maintenance of the antephase checkpoint that regulates cell cycle entry into mitosis and, therefore, may play a key role in cell cycle progression and tumorigenesis. The encoded protein has an N-terminal forkhead-associated domain, a central RING-finger domain, and a cysteine-rich C-terminal region. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF605	NM_183238.4	c.*3021C>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000360187.9	NP_899061.1
ZNF605	NM_001164715.2	c.*3021C>T		3_prime_UTR_variant	Exon 5 of 5		NP_001158187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF605	ENST00000360187.9	c.*3021C>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_183238.4	ENSP00000353314.3
ZNF605	ENST00000392321.3	c.*3021C>T		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000376135.3
CHFR	ENST00000536932.5	c.-252+23269C>T		intron_variant	Intron 2 of 5	4		ENSP00000475247.1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63273 AN: 151916 Hom.: 13966 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.473

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.416 AC: 63290 AN: 152034 Hom.: 13965 Cov.: 33 AF XY: 0.412 AC XY: 30644 AN XY: 74290

African (AFR) AF: 0.298 AC: 12344 AN: 41490

American (AMR) AF: 0.443 AC: 6757 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1873 AN: 3472

East Asian (EAS) AF: 0.219 AC: 1129 AN: 5162

South Asian (SAS) AF: 0.528 AC: 2545 AN: 4824

European-Finnish (FIN) AF: 0.359 AC: 3788 AN: 10550

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33165 AN: 67954

Other (OTH) AF: 0.474 AC: 1001 AN: 2110

Alfa AF: 0.447 Hom.: 3566

Bravo AF: 0.416

Asia WGS AF: 0.395 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.58
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs1278602; hg19: chr12-133498938;