NM_183238.4:c.*2478G>A

Variant names:

• chr12-132922895-C-T
• rs1278601
• NM_183238.4:c.*2478G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183238.4. 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
	ZNF605	NM_183238.4	MANE Select	c.*2478G>A		3_prime_UTR	Exon 5 of 5	NP_899061.1	Q86T29-1
	ZNF605	NM_001164715.2		c.*2478G>A		3_prime_UTR	Exon 5 of 5	NP_001158187.1	Q86T29-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF605	ENST00000360187.9	TSL:1 MANE Select	c.*2478G>A		3_prime_UTR	Exon 5 of 5	ENSP00000353314.3	Q86T29-1
	ZNF605	ENST00000392321.3	TSL:2	c.*2478G>A		3_prime_UTR	Exon 5 of 5	ENSP00000376135.3	Q86T29-2
	ZNF605	ENST00000920344.1		c.*2478G>A		3_prime_UTR	Exon 5 of 5	ENSP00000590403.1

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 1.00 AC: 2 AN: 2

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) AF: 0.300 AC: 6 AN: 20

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.343 AC: 14206 AN: 41452

American (AMR) AF: 0.446 AC: 6807 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1871 AN: 3464

East Asian (EAS) AF: 0.218 AC: 1126 AN: 5172

South Asian (SAS) AF: 0.528 AC: 2541 AN: 4812

European-Finnish (FIN) AF: 0.358 AC: 3791 AN: 10578

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

European-Non Finnish (NFE) AF: 0.488 AC: 33163 AN: 67954

Other (OTH) AF: 0.481 AC: 1012 AN: 2106

Alfa AF: 0.470 Hom.: 48714

Bravo AF: 0.430

Asia WGS AF: 0.398 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.70
PhyloP100		0.30
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: rs1278601; hg19: chr12-133499481;