7-101154529-G-A

Variant names:

• chr7-101154529-G-A
• NM_001283.5:c.3+12G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001283.5(AP1S1):​c.3+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000706 in 1,416,110 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: AP1S1 NM_001283.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0480
• Publications: 0 publications found

Genes affected

AP1S1 (HGNC:559): (adaptor related protein complex 1 subunit sigma 1) The protein encoded by this gene is part of the clathrin coat assembly complex which links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing. This protein, as well as beta-prime-adaptin, gamma-adaptin, and the medium (mu) chain AP47, form the AP-1 assembly protein complex located at the Golgi vesicle. [provided by RefSeq, Jul 2008]

AP1S1 Gene-Disease associations (from GenCC):

• MEDNIK syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.007).
• BP6: Variant 7-101154529-G-A is Benign according to our data. Variant chr7-101154529-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2725013.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001283.5. 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
	AP1S1	NM_001283.5	MANE Select	c.3+12G>A		intron	N/A	NP_001274.1	P61966-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP1S1	ENST00000337619.11	TSL:1 MANE Select	c.3+12G>A		intron	N/A	ENSP00000336666.5	P61966-1
	AP1S1	ENST00000429457.1	TSL:5	c.3G>A	p.Ala1Ala	synonymous	Exon 1 of 5	ENSP00000399902.1	H7C1E4
	AP1S1	ENST00000926144.1		c.3+12G>A		intron	N/A	ENSP00000596203.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.06e-7 AC: 1 AN: 1416110 Hom.: 0 Cov.: 33 AF XY: 0.00000143 AC XY: 1 AN XY: 700036

African (AFR) AF: 0.00 AC: 0 AN: 32500

American (AMR) AF: 0.00 AC: 0 AN: 37600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25330

East Asian (EAS) AF: 0.00 AC: 0 AN: 37380

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80440

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49934

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5020

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089286

Other (OTH) AF: 0.00 AC: 0 AN: 58620

GnomAD4 genome Cov.: 31

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	-0.42
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		-0.048
PromoterAI		-0.0020	Neutral

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

hg19: chr7-100797810;