chr19-11577093-G-A

Variant names:

• chr19-11577093-G-A
• rs62638747
• NM_001611.5:c.225C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001611.5(ACP5):​c.225C>T​(p.Phe75Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,984 control chromosomes in the GnomAD database, including 11,166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.094 (827 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10339 hom.)
• Consequence: ACP5 NM_001611.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.53
• Publications: 13 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: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 19-11577093-G-A is Benign according to our data. Variant chr19-11577093-G-A is described in ClinVar as Benign. ClinVar VariationId is 257477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

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.225C>T	p.Phe75Phe	synonymous	Exon 2 of 5	NP_001602.1	P13686
	ACP5	NM_001111034.3		c.225C>T	p.Phe75Phe	synonymous	Exon 3 of 6	NP_001104504.1	P13686
	ACP5	NM_001111035.3		c.225C>T	p.Phe75Phe	synonymous	Exon 4 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.225C>T	p.Phe75Phe	synonymous	Exon 2 of 5	ENSP00000496973.1	P13686
	ACP5	ENST00000218758.10	TSL:1	c.225C>T	p.Phe75Phe	synonymous	Exon 4 of 7	ENSP00000218758.4	P13686
	ACP5	ENST00000889667.1		c.225C>T	p.Phe75Phe	synonymous	Exon 2 of 5	ENSP00000559726.1

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14327 AN: 152076 Hom.: 826 Cov.: 32

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.0819

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0224

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.100 AC: 25254 AN: 251446 AF XY: 0.104

Gnomad AFR exome AF: 0.0383

Gnomad AMR exome AF: 0.0648

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.0206

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.116 AC: 169407 AN: 1461790 Hom.: 10339 Cov.: 35 AF XY: 0.116 AC XY: 84295 AN XY: 727198

African (AFR) AF: 0.0382 AC: 1280 AN: 33478

American (AMR) AF: 0.0689 AC: 3083 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3238 AN: 26134

East Asian (EAS) AF: 0.0247 AC: 981 AN: 39700

South Asian (SAS) AF: 0.0970 AC: 8367 AN: 86258

European-Finnish (FIN) AF: 0.150 AC: 8023 AN: 53418

Middle Eastern (MID) AF: 0.169 AC: 972 AN: 5768

European-Non Finnish (NFE) AF: 0.123 AC: 136725 AN: 1111916

Other (OTH) AF: 0.112 AC: 6738 AN: 60394

GnomAD4 genome AF: 0.0941 AC: 14327 AN: 152194 Hom.: 827 Cov.: 32 AF XY: 0.0937 AC XY: 6969 AN XY: 74392

African (AFR) AF: 0.0381 AC: 1584 AN: 41550

American (AMR) AF: 0.0818 AC: 1249 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3470

East Asian (EAS) AF: 0.0226 AC: 117 AN: 5166

South Asian (SAS) AF: 0.0866 AC: 418 AN: 4826

European-Finnish (FIN) AF: 0.156 AC: 1651 AN: 10602

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8446 AN: 67988

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.109 Hom.: 821

Bravo AF: 0.0873

Asia WGS AF: 0.0630 AC: 218 AN: 3478

EpiCase AF: 0.127

EpiControl AF: 0.130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Spondyloenchondrodysplasia with immune dysregulation (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.8
DANN	Benign	0.65
PhyloP100		2.5
PromoterAI		-0.039	Neutral
Mutation Taster		=94/6	polymorphism (auto)

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: rs62638747; hg19: chr19-11687908; COSMIC: COSV54536087; COSMIC: COSV54536087;