rs373030121

Variant names:

• chr19-11576285-G-A
• rs373030121
• NM_001611.5:c.693C>T
• ACP5 p.Tyr231Tyr

Your query was ambiguous. Multiple possible variants found:

• chr19-11576285-G-A
• chr19-11576285-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001611.5(ACP5):​c.693C>T​(p.Tyr231Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00071 in 1,610,394 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (18 hom.)
• Consequence: ACP5 NM_001611.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.79
• Publications: 3 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 19-11576285-G-A is Benign according to our data. Variant chr19-11576285-G-A is described in ClinVar as Benign. ClinVar VariationId is 464891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.79 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000322 (49/152272) while in subpopulation SAS AF = 0.00953 (46/4828). AF 95% confidence interval is 0.00734. There are 0 homozygotes in GnomAd4. There are 33 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 18 AR gene

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.693C>T	p.Tyr231Tyr	synonymous	Exon 4 of 5	NP_001602.1	P13686
	ACP5	NM_001111034.3		c.693C>T	p.Tyr231Tyr	synonymous	Exon 5 of 6	NP_001104504.1	P13686
	ACP5	NM_001111035.3		c.693C>T	p.Tyr231Tyr	synonymous	Exon 6 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.693C>T	p.Tyr231Tyr	synonymous	Exon 4 of 5	ENSP00000496973.1	P13686
	ACP5	ENST00000218758.10	TSL:1	c.693C>T	p.Tyr231Tyr	synonymous	Exon 6 of 7	ENSP00000218758.4	P13686
	ACP5	ENST00000889667.1		c.717C>T	p.Tyr239Tyr	synonymous	Exon 4 of 5	ENSP00000559726.1

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 50 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00161 AC: 400 AN: 247776 AF XY: 0.00223

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000354

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000751 AC: 1095 AN: 1458122 Hom.: 18 Cov.: 33 AF XY: 0.00107 AC XY: 777 AN XY: 725448

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44720

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0120 AC: 1037 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50400

Middle Eastern (MID) AF: 0.000384 AC: 2 AN: 5212

European-Non Finnish (NFE) AF: 0.0000144 AC: 16 AN: 1111978

Other (OTH) AF: 0.000647 AC: 39 AN: 60310

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33 AN XY: 74452

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00953 AC: 46 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.0000567

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Spondyloenchondrodysplasia with immune dysregulation (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.5
DANN	Benign	0.27
PhyloP100		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs373030121;

hg19: chr19-11687100;

COSMIC: COSV54536309;

COSMIC: COSV54536309;