NM_194320.4:c.640C>A

Variant names:

• chr9-94300198-C-A
• rs774957018
• NM_194320.4:c.640C>A

Variant summary

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

The NM_194320.4(ZNF169):​c.640C>A​(p.Arg214Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R214C) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF169 NM_194320.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 4 publications found

Genes affected

ZNF169 (HGNC:12957): (zinc finger protein 169) 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: 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 (MetaRNN=0.04790595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF169	NM_194320.4	c.640C>A	p.Arg214Ser	missense_variant	Exon 5 of 5	ENST00000395395.7	NP_919301.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF169	ENST00000395395.7	c.640C>A	p.Arg214Ser	missense_variant	Exon 5 of 5	2	NM_194320.4	ENSP00000378792.2
ZNF169	ENST00000718459.1	c.643C>A	p.Arg215Ser	missense_variant	Exon 5 of 5			ENSP00000520837.1
ZNF169	ENST00000340911.8	c.*629C>A		3_prime_UTR_variant	Exon 5 of 5	2		ENSP00000340711.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.5
DANN	Benign	0.71
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.081
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.010
Sift	Benign	0.39	T
Sift4G	Benign	0.40	T
Polyphen		0.0010	B
Vest4		0.057
MutPred		0.37		Loss of MoRF binding (P = 0.0094);
MVP		0.076
MPC		0.090
ClinPred		0.029	T
GERP RS		0.29
Varity_R		0.067
gMVP		0.060
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

dbSNP: rs774957018; hg19: chr9-97062480;