19-37347309-C-T

Variant names:

• chr19-37347309-C-T
• rs115422824
• NM_001353803.2:c.153C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001353803.2(ZNF875):​c.153C>T​(p.Val51Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,613,004 control chromosomes in the GnomAD database, including 304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (175 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (129 hom.)
• Consequence: ZNF875 NM_001353803.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.876
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 19-37347309-C-T is Benign according to our data. Variant chr19-37347309-C-T is described in ClinVar as Benign. ClinVar VariationId is 787490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.876 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353803.2. 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.153C>T	p.Val51Val	synonymous	Exon 3 of 5	NP_001340732.1	P10072-2
	ZNF875	NM_181786.4		c.210C>T	p.Val70Val	synonymous	Exon 4 of 6	NP_861451.1	P10072-1
	ZNF875	NM_001329761.2		c.153C>T	p.Val51Val	synonymous	Exon 3 of 5	NP_001316690.1	K7EPW3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF875	ENST00000392153.8	TSL:1 MANE Select	c.153C>T	p.Val51Val	synonymous	Exon 3 of 5	ENSP00000375994.3	P10072-2
	ZNF875	ENST00000324411.8	TSL:1	c.210C>T	p.Val70Val	synonymous	Exon 4 of 6	ENSP00000315505.3	P10072-1
	ZNF875	ENST00000541583.6	TSL:1	c.27C>T	p.Val9Val	synonymous	Exon 2 of 4	ENSP00000438261.1	Q7Z6E1

Frequencies

GnomAD3 genomes AF: 0.0247 AC: 3755 AN: 152198 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0191

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.00691 AC: 1726 AN: 249902 AF XY: 0.00505

Gnomad AFR exome AF: 0.0913

Gnomad AMR exome AF: 0.00609

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000142

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00247 AC: 3615 AN: 1460688 Hom.: 129 Cov.: 30 AF XY: 0.00208 AC XY: 1515 AN XY: 726634

African (AFR) AF: 0.0859 AC: 2875 AN: 33456

American (AMR) AF: 0.00674 AC: 301 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25978

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.0000855 AC: 95 AN: 1111304

Other (OTH) AF: 0.00520 AC: 314 AN: 60352

GnomAD4 genome AF: 0.0247 AC: 3755 AN: 152316 Hom.: 175 Cov.: 32 AF XY: 0.0240 AC XY: 1785 AN XY: 74492

African (AFR) AF: 0.0850 AC: 3532 AN: 41548

American (AMR) AF: 0.0107 AC: 164 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68034

Other (OTH) AF: 0.0204 AC: 43 AN: 2112

Alfa AF: 0.0128 Hom.: 42

Bravo AF: 0.0286

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.6
DANN	Benign	0.68
PhyloP100		0.88
PromoterAI		-0.0052	Neutral
Mutation Taster		=299/1	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: rs115422824; hg19: chr19-37838211;