rs1278601

Positions:

• chr12-132922895-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183238.4(ZNF605):​c.*2478G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 152,040 control chromosomes in the GnomAD database, including 14,635 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 0.43 (14632 hom., cov: 32)
  • Exomes 𝑓: 0.35 (3 hom.)
• Consequence: ZNF605 NM_183238.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF605	NM_183238.4	c.*2478G>A		3_prime_UTR_variant	5/5	ENST00000360187.9	NP_899061.1
ZNF605	NM_001164715.2	c.*2478G>A		3_prime_UTR_variant	5/5		NP_001158187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF605	ENST00000360187	c.*2478G>A		3_prime_UTR_variant	5/5	1	NM_183238.4	ENSP00000353314.3
ZNF605	ENST00000392321	c.*2478G>A		3_prime_UTR_variant	5/5	2		ENSP00000376135.3
CHFR	ENST00000536932.5	c.-252+22726G>A		intron_variant		4		ENSP00000475247.1

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65176 AN: 151896 Hom.: 14625 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.479

GnomAD4 exome AF: 0.346 AC: 9 AN: 26 Hom.: 3 Cov.: 0 AF XY: 0.350 AC XY: 7 AN XY: 20

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 1.00

Gnomad4 NFE exome AF: 0.300

GnomAD4 genome AF: 0.429 AC: 65202 AN: 152014 Hom.: 14632 Cov.: 32 AF XY: 0.425 AC XY: 31563 AN XY: 74322

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.481

Alfa AF: 0.482 Hom.: 31190

Bravo AF: 0.430

Asia WGS AF: 0.398 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.70

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: rs1278601; hg19: chr12-133499481;