chr19-36183029-C-A

Variant names:

• chr19-36183029-C-A
• NM_152477.5:c.937G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_152477.5(ZNF565):​c.937G>T​(p.Gly313Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G313R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF565 NM_152477.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.36

Genes affected

ZNF565 (HGNC:26726): (zinc finger protein 565) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF565	NM_152477.5	c.937G>T	p.Gly313Trp	missense_variant	Exon 5 of 5	ENST00000304116.10	NP_689690.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF565	ENST00000304116.10	c.937G>T	p.Gly313Trp	missense_variant	Exon 5 of 5	2	NM_152477.5	ENSP00000306869.5
ZNF565	ENST00000591473.1	c.742G>T	p.Gly248Trp	missense_variant	Exon 4 of 4	1		ENSP00000465906.1
ZNF565	ENST00000355114.9	c.1057G>T	p.Gly353Trp	missense_variant	Exon 5 of 5	2		ENSP00000347234.5
ZNF565	ENST00000392173.6	c.937G>T	p.Gly313Trp	missense_variant	Exon 5 of 5	2		ENSP00000376013.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	.;.;T;.
Eigen	Pathogenic	0.79
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.22	T;.;T;T
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.84	D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.8	H;H;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-7.3	D;D;D;.
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;.
Vest4		0.46
MutPred		0.60		Gain of catalytic residue at G313 (P = 0.0029);Gain of catalytic residue at G313 (P = 0.0029);.;.;
MVP		0.91
MPC		1.3
ClinPred		1.0	D
GERP RS		4.6
Varity_R		0.68
gMVP		0.077

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-36673931;