19-12272922-C-T

Variant names:

• chr19-12272922-C-T
• rs777251487
• NM_016264.4:c.1333G>A

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.1333G>A​(p.Gly445Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ZNF44 NM_016264.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.970
• 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=0.16091314).

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.1333G>A	p.Gly445Arg	missense	Exon 4 of 4	NP_057348.3	F8W7T7
	ZNF44	NM_001164276.2		c.1477G>A	p.Gly493Arg	missense	Exon 5 of 5	NP_001157748.1	P15621-1
	ZNF44	NM_001353549.2		c.1237G>A	p.Gly413Arg	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.1333G>A	p.Gly445Arg	missense	Exon 4 of 4	ENSP00000347910.5	F8W7T7
	ZNF44	ENST00000393337.7	TSL:1	n.1477G>A		non_coding_transcript_exon	Exon 5 of 8	ENSP00000377008.3	P15621-3
	ZNF44	ENST00000356109.10	TSL:2	c.1477G>A	p.Gly493Arg	missense	Exon 5 of 5	ENSP00000348419.5	P15621-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000240 AC: 6 AN: 250186 AF XY: 0.0000221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000217

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461862 Hom.: 0 Cov.: 35 AF XY: 0.00000550 AC XY: 4 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39694

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

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	0.18
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.00067	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.97
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-6.8	D
REVEL	Benign	0.088
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.028	D
Polyphen		1.0	D
Vest4		0.13
MutPred		0.36		Gain of solvent accessibility (P = 0.0037)
MVP		0.32
MPC		0.40
ClinPred		0.72	D
GERP RS		-0.22
Varity_R		0.38
gMVP		0.021
Mutation Taster		=92/8	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: rs777251487; hg19: chr19-12383737; COSMIC: COSV104660966; COSMIC: COSV104660966;