19-43597119-C-T

Variant names:

• chr19-43597119-C-T
• rs1342837087
• NM_001145347.2:c.11C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145347.2(ZNF576):​c.11C>T​(p.Pro4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,068 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P4Q) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: ZNF576 NM_001145347.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 0 publications found

Genes affected

ZNF576 (HGNC:28357): (zinc finger protein 576) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and 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]

SRRM5 (HGNC:37248): (serine/arginine repetitive matrix 5)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.025643796).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145347.2. 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
	ZNF576	NM_001145347.2	MANE Select	c.11C>T	p.Pro4Leu	missense	Exon 2 of 3	NP_001138819.1	Q9H609
	ZNF576	NM_024327.2		c.11C>T	p.Pro4Leu	missense	Exon 2 of 3	NP_077303.1	Q9H609

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF576	ENST00000336564.5	TSL:1 MANE Select	c.11C>T	p.Pro4Leu	missense	Exon 2 of 3	ENSP00000337852.4	Q9H609
	SRRM5	ENST00000607544.1	TSL:2	c.-170C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	ENSP00000476253.1	B3KS81
	ZNF576	ENST00000391965.6	TSL:2	c.11C>T	p.Pro4Leu	missense	Exon 2 of 3	ENSP00000375827.2	Q9H609

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152068 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74268

African (AFR) AF: 0.0000483 AC: 2 AN: 41388

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.3
DANN	Benign	0.84
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.14
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.062
Sift	Benign	1.0	T
Sift4G	Uncertain	0.037	D
Polyphen		0.0010	B
Vest4		0.084
MutPred		0.27		Loss of sheet (P = 0.0483)
MVP		0.26
MPC		0.57
ClinPred		0.046	T
GERP RS		-1.9
Varity_R		0.022
gMVP		0.25
Mutation Taster		=98/2	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: rs1342837087; hg19: chr19-44101271;