NM_032493.4:c.342G>C

Variant names:

• chr19-16208093-G-C
• rs143435975
• NM_032493.4:c.342G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_032493.4(AP1M1):​c.342G>C​(p.Leu114Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00628 in 1,613,898 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0045 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (47 hom.)
• Consequence: AP1M1 NM_032493.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.17
• Publications: 2 publications found

Genes affected

AP1M1 (HGNC:13667): (adaptor related protein complex 1 subunit mu 1) The protein encoded by this gene is the medium chain of the trans-Golgi network clathrin-associated protein complex AP-1. The other components of this complex are beta-prime-adaptin, gamma-adaptin, and the small chain AP1S1. This complex is located at the Golgi vesicle and links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing. Alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 19-16208093-G-C is Benign according to our data. Variant chr19-16208093-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2649508.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.17 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032493.4. 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
	AP1M1	NM_032493.4	MANE Select	c.342G>C	p.Leu114Leu	synonymous	Exon 4 of 12	NP_115882.1	Q9BXS5-1
	AP1M1	NM_001130524.2		c.342G>C	p.Leu114Leu	synonymous	Exon 4 of 13	NP_001123996.1	Q9BXS5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1M1	ENST00000291439.8	TSL:1 MANE Select	c.342G>C	p.Leu114Leu	synonymous	Exon 4 of 12	ENSP00000291439.2	Q9BXS5-1
	AP1M1	ENST00000444449.6	TSL:1	c.342G>C	p.Leu114Leu	synonymous	Exon 4 of 13	ENSP00000388996.1	Q9BXS5-2
	AP1M1	ENST00000908210.1		c.342G>C	p.Leu114Leu	synonymous	Exon 4 of 13	ENSP00000578269.1

Frequencies

GnomAD3 genomes AF: 0.00454 AC: 691 AN: 152082 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000721

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00593

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00499 AC: 1255 AN: 251394 AF XY: 0.00486

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00268

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.00559

Gnomad OTH exome AF: 0.00636

GnomAD4 exome AF: 0.00646 AC: 9439 AN: 1461698 Hom.: 47 Cov.: 31 AF XY: 0.00631 AC XY: 4589 AN XY: 727168

African (AFR) AF: 0.000747 AC: 25 AN: 33480

American (AMR) AF: 0.00107 AC: 48 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00341 AC: 89 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00179 AC: 154 AN: 86252

European-Finnish (FIN) AF: 0.0202 AC: 1081 AN: 53390

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.00685 AC: 7618 AN: 1111894

Other (OTH) AF: 0.00697 AC: 421 AN: 60386

GnomAD4 genome AF: 0.00454 AC: 691 AN: 152200 Hom.: 2 Cov.: 32 AF XY: 0.00485 AC XY: 361 AN XY: 74420

African (AFR) AF: 0.00106 AC: 44 AN: 41530

American (AMR) AF: 0.000720 AC: 11 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5180

South Asian (SAS) AF: 0.000623 AC: 3 AN: 4812

European-Finnish (FIN) AF: 0.0198 AC: 210 AN: 10602

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

European-Non Finnish (NFE) AF: 0.00593 AC: 403 AN: 68002

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00477 Hom.: 2

Bravo AF: 0.00318

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00595

EpiControl AF: 0.00539

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	8.2
DANN	Benign	0.68
PhyloP100		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=95/5	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: rs143435975; hg19: chr19-16318904; COSMIC: COSV99358676; COSMIC: COSV99358676;