rs747744356

Variant names:

• chr19-36182986-C-A
• rs747744356
• NM_152477.5:c.980G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-36182986-C-A
• chr19-36182986-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152477.5(ZNF565):​c.980G>T​(p.Arg327Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R327Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF565 NM_152477.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF565	NM_152477.5	c.980G>T	p.Arg327Leu	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.980G>T	p.Arg327Leu	missense_variant	Exon 5 of 5	2	NM_152477.5	ENSP00000306869.5
ZNF565	ENST00000355114.9	c.1100G>T	p.Arg367Leu	missense_variant	Exon 5 of 5	2		ENSP00000347234.5
ZNF565	ENST00000392173.6	c.980G>T	p.Arg327Leu	missense_variant	Exon 5 of 5	2		ENSP00000376013.1
ZNF565	ENST00000591473.1	c.*6G>T		downstream_gene_variant		1		ENSP00000465906.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251438 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135900

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;.;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.21	T;.;T
M_CAP	Benign	0.0049	T
MetaRNN	Uncertain	0.50	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.6	D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.016	D;D;D
Vest4		0.56
MutPred		0.60		Loss of MoRF binding (P = 0.0209);Loss of MoRF binding (P = 0.0209);.;
MVP		0.45
MPC		1.2
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.53
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs747744356; hg19: chr19-36673888;