rs745604493

Variant names:

• chr19-11575029-G-A
• rs745604493
• NM_001611.5:c.959C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-11575029-G-A
• chr19-11575029-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001611.5(ACP5):​c.959C>T​(p.Pro320Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000109 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P320P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: ACP5 NM_001611.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.64
• Publications: 2 publications found

Genes affected

ACP5 (HGNC:124): (acid phosphatase 5, tartrate resistant) This gene encodes an iron containing glycoprotein which catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is the most basic of the acid phosphatases and is the only form not inhibited by L(+)-tartrate. [provided by RefSeq, Aug 2008]

ZNF627 (HGNC:30570): (zinc finger protein 627) 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]

LOC124904638 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4073741).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001611.5. 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
	ACP5	NM_001611.5	MANE Select	c.959C>T	p.Pro320Leu	missense	Exon 5 of 5	NP_001602.1	P13686
	ACP5	NM_001111034.3		c.959C>T	p.Pro320Leu	missense	Exon 6 of 6	NP_001104504.1	P13686
	ACP5	NM_001111035.3		c.959C>T	p.Pro320Leu	missense	Exon 7 of 7	NP_001104505.1	P13686

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP5	ENST00000648477.1	MANE Select	c.959C>T	p.Pro320Leu	missense	Exon 5 of 5	ENSP00000496973.1	P13686
	ACP5	ENST00000218758.10	TSL:1	c.959C>T	p.Pro320Leu	missense	Exon 7 of 7	ENSP00000218758.4	P13686
	ACP5	ENST00000889667.1		c.983C>T	p.Pro328Leu	missense	Exon 5 of 5	ENSP00000559726.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 250938 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 16 AN: 1461810 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727200

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	Spondyloenchondrodysplasia with immune dysregulation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.075	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.010
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.6
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.28
Sift	Benign	0.076	T
Sift4G	Uncertain	0.0060	D
Polyphen		0.27	B
Vest4		0.44
MutPred		0.36		Gain of sheet (P = 0.0073)
MVP		0.82
MPC		0.96
ClinPred		0.91	D
GERP RS		5.1
Varity_R		0.16
gMVP		0.55
Mutation Taster		=60/40	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: rs745604493; hg19: chr19-11685844; COSMIC: COSV54535093; COSMIC: COSV54535093;