19-12272531-C-G

Variant names:

• chr19-12272531-C-G
• NM_016264.4:c.1724G>C

Variant summary

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

The NM_016264.4(ZNF44):​c.1724G>C​(p.Cys575Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF44 NM_016264.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.285
• Publications: 0 publications found

Genes affected

ZNF44 (HGNC:13110): (zinc finger protein 44) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [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=0.13693422).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016264.4. 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
	ZNF44	NM_016264.4	MANE Select	c.1724G>C	p.Cys575Ser	missense	Exon 4 of 4	NP_057348.3	F8W7T7
	ZNF44	NM_001164276.2		c.1868G>C	p.Cys623Ser	missense	Exon 5 of 5	NP_001157748.1	P15621-1
	ZNF44	NM_001353549.2		c.1628G>C	p.Cys543Ser	missense	Exon 6 of 6	NP_001340478.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF44	ENST00000355684.6	TSL:2 MANE Select	c.1724G>C	p.Cys575Ser	missense	Exon 4 of 4	ENSP00000347910.5	F8W7T7
	ZNF44	ENST00000393337.7	TSL:1	n.1868G>C		non_coding_transcript_exon	Exon 5 of 8	ENSP00000377008.3	P15621-3
	ZNF44	ENST00000356109.10	TSL:2	c.1868G>C	p.Cys623Ser	missense	Exon 5 of 5	ENSP00000348419.5	P15621-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

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	0.71
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.7
DANN	Benign	0.92
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.000060	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.10	N
PhyloP100		-0.28
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.034
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.25	B
Vest4		0.20
MutPred		0.52		Gain of phosphorylation at C623 (P = 0.0132)
MVP		0.42
MPC		0.18
ClinPred		0.19	T
GERP RS		-0.20
Varity_R		0.26
gMVP		0.058
Mutation Taster		=99/1	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: chr19-12383346;