19-22089941-G-T

Variant names:

• chr19-22089941-G-T
• rs9304994
• NM_033468.4:c.*499G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033468.4(ZNF257):​c.*499G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: ZNF257 NM_033468.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 11 publications found

Genes affected

ZNF257 (HGNC:13498): (zinc finger protein 257) 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]

ENSG00000308832 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033468.4. 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
	ZNF257	NM_033468.4	MANE Select	c.*499G>T		3_prime_UTR	Exon 4 of 4	NP_258429.2	Q9Y2Q1-1
	ZNF257	NM_001316996.2		c.*499G>T		3_prime_UTR	Exon 5 of 5	NP_001303925.1	Q9Y2Q1-3
	ZNF257	NM_001316997.2		c.*499G>T		3_prime_UTR	Exon 5 of 5	NP_001303926.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF257	ENST00000594947.6	TSL:4 MANE Select	c.*499G>T		3_prime_UTR	Exon 4 of 4	ENSP00000470209.1	Q9Y2Q1-1
	ZNF257	ENST00000435820.6	TSL:1	n.*2204G>T		non_coding_transcript_exon	Exon 5 of 5	ENSP00000406147.2	M0R321
	ZNF257	ENST00000435820.6	TSL:1	n.*2204G>T		3_prime_UTR	Exon 5 of 5	ENSP00000406147.2	M0R321

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.36
DANN	Benign	0.16
PhyloP100		-0.19

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: rs9304994; hg19: chr19-22272743;