19-37347204-C-A

Variant names:

• chr19-37347204-C-A
• rs1296043847
• NM_001353803.2:c.48C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001353803.2(ZNF875):​c.48C>A​(p.Phe16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF875 NM_001353803.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.264
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.48C>A	p.Phe16Leu	missense	Exon 3 of 5	NP_001340732.1	P10072-2
	ZNF875	NM_181786.4		c.105C>A	p.Phe35Leu	missense	Exon 4 of 6	NP_861451.1	P10072-1
	ZNF875	NM_001329761.2		c.48C>A	p.Phe16Leu	missense	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.48C>A	p.Phe16Leu	missense	Exon 3 of 5	ENSP00000375994.3	P10072-2
	ZNF875	ENST00000324411.8	TSL:1	c.105C>A	p.Phe35Leu	missense	Exon 4 of 6	ENSP00000315505.3	P10072-1
	ZNF875	ENST00000591259.5	TSL:1	c.48C>A	p.Phe16Leu	missense	Exon 3 of 5	ENSP00000466472.1	K7EME6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0032	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.26
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.21
Sift	Uncertain	0.023	D
Sift4G	Benign	0.29	T
Polyphen		1.0	D
Vest4		0.73
MutPred		0.79		Loss of catalytic residue at R36 (P = 0.1924)
MVP		0.34
MPC		0.034
ClinPred		0.83	D
GERP RS		2.4
PromoterAI		-0.0035	Neutral
Varity_R		0.17
gMVP		0.20
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1296043847; hg19: chr19-37838106;