7-149103647-C-A

Variant names:

• chr7-149103647-C-A
• NM_001001661.3:c.2224G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001001661.3(ZNF425):​c.2224G>T​(p.Ala742Ser) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF425 NM_001001661.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.209
• Publications: 0 publications found

Genes affected

ZNF425 (HGNC:20690): (zinc finger protein 425) Predicted to enable DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription, DNA-templated. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09172073).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001661.3. 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
	ZNF425	NM_001001661.3	MANE Select	c.2224G>T	p.Ala742Ser	missense	Exon 4 of 4	NP_001001661.1	Q6IV72

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF425	ENST00000378061.7	TSL:1 MANE Select	c.2224G>T	p.Ala742Ser	missense	Exon 4 of 4	ENSP00000367300.2	Q6IV72
	ZNF425	ENST00000926832.1		c.2203G>T	p.Ala735Ser	missense	Exon 4 of 4	ENSP00000596891.1
	ZNF425	ENST00000951283.1		c.2065G>T	p.Ala689Ser	missense	Exon 3 of 3	ENSP00000621342.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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	Benign	0.11
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.0
DANN	Benign	0.77
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.089	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.00099	T
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.64	N
PhyloP100		-0.21
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.076
Sift	Benign	0.15	T
Sift4G	Benign	0.25	T
Polyphen		0.028	B
Vest4		0.053
MutPred		0.41		Gain of disorder (P = 0.034)
MVP		0.30
MPC		0.29
ClinPred		0.046	T
GERP RS		-0.38
Varity_R		0.045
gMVP		0.018
Mutation Taster		=100/0	polymorphism

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

hg19: chr7-148800739;