rs117205129

Variant names:

• chr20-51604848-G-A
• rs117205129
• NM_006045.3:c.2976C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-51604848-G-A
• chr20-51604848-G-C
• chr20-51604848-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_006045.3(ATP9A):​c.2976C>T​(p.Ile992Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00182 in 1,547,294 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (57 hom.)
• Consequence: ATP9A NM_006045.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.322
• Publications: 4 publications found

Genes affected

ATP9A (HGNC:13540): (ATPase phospholipid transporting 9A (putative)) Enables protease binding activity. Involved in negative regulation of exosomal secretion; regulation of endocytic recycling; and regulation of retrograde transport, endosome to Golgi. Located in several cellular components, including endosome membrane; perinuclear region of cytoplasm; and trans-Golgi network membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATP9A Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with poor growth and behavioral abnormalities

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 20-51604848-G-A is Benign according to our data. Variant chr20-51604848-G-A is described in ClinVar as Benign. ClinVar VariationId is 770302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.322 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00369 (562/152316) while in subpopulation AMR AF = 0.0286 (438/15290). AF 95% confidence interval is 0.0264. There are 9 homozygotes in GnomAd4. There are 306 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006045.3. 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
	ATP9A	NM_006045.3	MANE Select	c.2976C>T	p.Ile992Ile	synonymous	Exon 27 of 28	NP_006036.1	O75110-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP9A	ENST00000338821.6	TSL:1 MANE Select	c.2976C>T	p.Ile992Ile	synonymous	Exon 27 of 28	ENSP00000342481.5	O75110-1
	ATP9A	ENST00000311637.9	TSL:1	c.2568C>T	p.Ile856Ile	synonymous	Exon 22 of 23	ENSP00000309086.5	A0A0A0MR22
	ATP9A	ENST00000892203.1		c.2862C>T	p.Ile954Ile	synonymous	Exon 26 of 27	ENSP00000562262.1

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 561 AN: 152198 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00744 AC: 1485 AN: 199712 AF XY: 0.00565

Gnomad AFR exome AF: 0.000672

Gnomad AMR exome AF: 0.0462

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0158

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000322

Gnomad OTH exome AF: 0.00774

GnomAD4 exome AF: 0.00161 AC: 2252 AN: 1394978 Hom.: 57 Cov.: 30 AF XY: 0.00143 AC XY: 987 AN XY: 689792

African (AFR) AF: 0.000361 AC: 11 AN: 30466

American (AMR) AF: 0.0447 AC: 1662 AN: 37170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22780

East Asian (EAS) AF: 0.00902 AC: 325 AN: 36040

South Asian (SAS) AF: 0.000454 AC: 35 AN: 77176

European-Finnish (FIN) AF: 0.0000387 AC: 2 AN: 51666

Middle Eastern (MID) AF: 0.000183 AC: 1 AN: 5466

European-Non Finnish (NFE) AF: 0.0000734 AC: 79 AN: 1076794

Other (OTH) AF: 0.00239 AC: 137 AN: 57420

GnomAD4 genome AF: 0.00369 AC: 562 AN: 152316 Hom.: 9 Cov.: 32 AF XY: 0.00411 AC XY: 306 AN XY: 74466

African (AFR) AF: 0.000914 AC: 38 AN: 41584

American (AMR) AF: 0.0286 AC: 438 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5178

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

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

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68036

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00257 Hom.: 9

Bravo AF: 0.00634

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	8.1
DANN	Benign	0.79
PhyloP100		0.32
Mutation Taster		=93/7	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: rs117205129; hg19: chr20-50221387;