rs592297

Variant names:

• chr11-86014894-C-T
• rs592297
• NM_007166.4:c.522G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-86014894-C-T
• chr11-86014894-C-A
• chr11-86014894-C-G

Variant summary

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

The NM_007166.4(PICALM):​c.522G>A​(p.Gln174Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,569,742 control chromosomes in the GnomAD database, including 499,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (50869 hom., cov: 32)
  • Exomes 𝑓: 0.79 (449073 hom.)
• Consequence: PICALM NM_007166.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.238
• Publications: 43 publications found

Genes affected

PICALM (HGNC:15514): (phosphatidylinositol binding clathrin assembly protein) This gene encodes a clathrin assembly protein, which recruits clathrin and adaptor protein complex 2 (AP2) to cell membranes at sites of coated-pit formation and clathrin-vesicle assembly. The protein may be required to determine the amount of membrane to be recycled, possibly by regulating the size of the clathrin cage. The protein is involved in AP2-dependent clathrin-mediated endocytosis at the neuromuscular junction. A chromosomal translocation t(10;11)(p13;q14) leading to the fusion of this gene and the MLLT10 gene is found in acute lymphoblastic leukemia, acute myeloid leukemia and malignant lymphomas. The polymorphisms of this gene are associated with the risk of Alzheimer disease. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 11-86014894-C-T is Benign according to our data. Variant chr11-86014894-C-T is described in ClinVar as Benign. ClinVar VariationId is 403299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.238 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007166.4. 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
	PICALM	NM_007166.4	MANE Select	c.522G>A	p.Gln174Gln	synonymous	Exon 5 of 20	NP_009097.2	Q13492-1
	PICALM	NM_001206946.2		c.522G>A	p.Gln174Gln	synonymous	Exon 5 of 20	NP_001193875.1	Q13492-5
	PICALM	NM_001411034.1		c.522G>A	p.Gln174Gln	synonymous	Exon 5 of 19	NP_001397963.1	Q13492-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PICALM	ENST00000393346.8	TSL:1 MANE Select	c.522G>A	p.Gln174Gln	synonymous	Exon 5 of 20	ENSP00000377015.3	Q13492-1
	PICALM	ENST00000526033.5	TSL:1	c.522G>A	p.Gln174Gln	synonymous	Exon 5 of 20	ENSP00000433846.1	Q13492-5
	PICALM	ENST00000532317.5	TSL:1	c.522G>A	p.Gln174Gln	synonymous	Exon 5 of 20	ENSP00000436958.1	Q13492-3

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124082 AN: 152036 Hom.: 50826 Cov.: 32

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.791

GnomAD2 exomes AF: 0.779 AC: 186043 AN: 238928 AF XY: 0.778

Gnomad AFR exome AF: 0.888

Gnomad AMR exome AF: 0.743

Gnomad ASJ exome AF: 0.737

Gnomad EAS exome AF: 0.677

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.798

Gnomad OTH exome AF: 0.790

GnomAD4 exome AF: 0.795 AC: 1126620 AN: 1417588 Hom.: 449073 Cov.: 24 AF XY: 0.793 AC XY: 560746 AN XY: 707082

African (AFR) AF: 0.893 AC: 28646 AN: 32082

American (AMR) AF: 0.745 AC: 31716 AN: 42552

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 19035 AN: 25698

East Asian (EAS) AF: 0.696 AC: 26901 AN: 38640

South Asian (SAS) AF: 0.735 AC: 61185 AN: 83296

European-Finnish (FIN) AF: 0.820 AC: 43257 AN: 52752

Middle Eastern (MID) AF: 0.765 AC: 4340 AN: 5676

European-Non Finnish (NFE) AF: 0.802 AC: 864951 AN: 1078102

Other (OTH) AF: 0.792 AC: 46589 AN: 58790

GnomAD4 genome AF: 0.816 AC: 124182 AN: 152154 Hom.: 50869 Cov.: 32 AF XY: 0.813 AC XY: 60426 AN XY: 74362

African (AFR) AF: 0.889 AC: 36913 AN: 41544

American (AMR) AF: 0.781 AC: 11949 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2602 AN: 3466

East Asian (EAS) AF: 0.683 AC: 3536 AN: 5176

South Asian (SAS) AF: 0.733 AC: 3535 AN: 4824

European-Finnish (FIN) AF: 0.821 AC: 8696 AN: 10586

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54480 AN: 67950

Other (OTH) AF: 0.789 AC: 1664 AN: 2108

Alfa AF: 0.802 Hom.: 30467

Bravo AF: 0.814

Asia WGS AF: 0.701 AC: 2438 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	PICALM-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	5.2
DANN	Benign	0.65
PhyloP100		0.24
Mutation Taster		=100/0	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: rs592297; hg19: chr11-85725937; COSMIC: COSV62672141;