7-101156606-C-T

Variant names:

• chr7-101156606-C-T
• rs189658039
• NM_001283.5:c.16C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_001283.5(AP1S1):​c.16C>T​(p.Leu6Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,611,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L6L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (1 hom.)
• Consequence: AP1S1 NM_001283.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.631
• 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Orphanet, Illumina

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 7-101156606-C-T is Benign according to our data. Variant chr7-101156606-C-T is described in ClinVar as Benign. ClinVar VariationId is 725419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000525 (80/152332) while in subpopulation AFR AF = 0.00183 (76/41582). AF 95% confidence interval is 0.0015. There are 0 homozygotes in GnomAd4. There are 46 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.16C>T	p.Leu6Leu	synonymous	Exon 2 of 5	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.16C>T	p.Leu6Leu	synonymous	Exon 2 of 5	ENSP00000336666.5	P61966-1
	AP1S1	ENST00000429457.1	TSL:5	c.139C>T	p.Leu47Leu	synonymous	Exon 2 of 5	ENSP00000399902.1	H7C1E4
	AP1S1	ENST00000926144.1		c.16C>T	p.Leu6Leu	synonymous	Exon 2 of 5	ENSP00000596203.1

Frequencies

GnomAD3 genomes AF: 0.000519 AC: 79 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000163 AC: 40 AN: 245648 AF XY: 0.0000751

Gnomad AFR exome AF: 0.00213

Gnomad AMR exome AF: 0.000234

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000582 AC: 85 AN: 1459660 Hom.: 1 Cov.: 30 AF XY: 0.0000468 AC XY: 34 AN XY: 725814

African (AFR) AF: 0.00191 AC: 64 AN: 33426

American (AMR) AF: 0.000225 AC: 10 AN: 44466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 85542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111116

Other (OTH) AF: 0.000182 AC: 11 AN: 60324

GnomAD4 genome AF: 0.000525 AC: 80 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.000618 AC XY: 46 AN XY: 74492

African (AFR) AF: 0.00183 AC: 76 AN: 41582

American (AMR) AF: 0.000196 AC: 3 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.000296 Hom.: 0

Bravo AF: 0.000672

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.44
CADD	Benign	19
DANN	Benign	0.78
PhyloP100		0.63
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.42		Position offset: 11

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs189658039; hg19: chr7-100799887;