19-57443615-A-G

Variant names:

• chr19-57443615-A-G
• rs181745270
• NM_001023561.4:c.467A>G

Variant summary

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

The NM_001023561.4(ZNF749):​c.467A>G​(p.Gln156Arg) 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. Q156L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF749 NM_001023561.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.577
• Publications: 1 publications found

Genes affected

ZNF749 (HGNC:32783): (zinc finger protein 749) 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]

ENSG00000268163 (HGNC:):

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=0.1132527).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF749	NM_001023561.4	c.467A>G	p.Gln156Arg	missense_variant	Exon 3 of 3	ENST00000334181.5	NP_001018855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF749	ENST00000334181.5	c.467A>G	p.Gln156Arg	missense_variant	Exon 3 of 3	2	NM_001023561.4	ENSP00000333980.4
ENSG00000268163	ENST00000596831.1	c.348-5523T>C		intron_variant	Intron 5 of 5	2		ENSP00000470969.1
ZNF749	ENST00000415248.1	c.*8A>G		downstream_gene_variant		4		ENSP00000397745.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 251332 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.41
DANN	Benign	0.78
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.022	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.93	L
PhyloP100		0.58
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.044
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.016	D
Polyphen		0.0010	B
Vest4		0.030
MutPred		0.46		Loss of ubiquitination at K159 (P = 0.0527);
MVP		0.25
MPC		0.033
ClinPred		0.051	T
GERP RS		-0.36
Varity_R		0.062
gMVP		0.012
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: rs181745270; hg19: chr19-57954983;