rs772023763

Variant names:

• chr19-37359643-C-T
• rs772023763
• ENST00000591259.5:c.474C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001353804.2(ZNF875):​c.474C>T​(p.Ile158Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZNF875 NM_001353804.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29
• Publications: 0 publications found

Genes affected

ZNF875 (HGNC:4928): (zinc finger protein 875) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 19-37359643-C-T is Benign according to our data. Variant chr19-37359643-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2672759.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.29 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353804.2. 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
	ZNF875	NM_001353803.2	MANE Select	c.257-2466C>T		intron	N/A	NP_001340732.1	P10072-2
	ZNF875	NM_001353804.2		c.474C>T	p.Ile158Ile	synonymous	Exon 5 of 5	NP_001340733.1	K7EME6
	ZNF875	NM_181786.4		c.314-2466C>T		intron	N/A	NP_861451.1	P10072-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF875	ENST00000591259.5	TSL:1	c.474C>T	p.Ile158Ile	synonymous	Exon 5 of 5	ENSP00000466472.1	K7EME6
	ZNF875	ENST00000392153.8	TSL:1 MANE Select	c.257-2466C>T		intron	N/A	ENSP00000375994.3	P10072-2
	ZNF875	ENST00000324411.8	TSL:1	c.314-2466C>T		intron	N/A	ENSP00000315505.3	P10072-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 148122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 45050 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 27290

African (AFR) AF: 0.00 AC: 0 AN: 420

American (AMR) AF: 0.00 AC: 0 AN: 986

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 916

East Asian (EAS) AF: 0.00 AC: 0 AN: 484

South Asian (SAS) AF: 0.00 AC: 0 AN: 11028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 184

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26202

Other (OTH) AF: 0.00 AC: 0 AN: 2010

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 148122 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72206

African (AFR) AF: 0.00 AC: 0 AN: 40132

American (AMR) AF: 0.00 AC: 0 AN: 14376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3422

East Asian (EAS) AF: 0.00 AC: 0 AN: 4630

South Asian (SAS) AF: 0.00 AC: 0 AN: 4496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67270

Other (OTH) AF: 0.00 AC: 0 AN: 2042

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs772023763; hg19: chr19-37850545;