NM_001353812.2:c.3288+7A>G

Variant names:

• chrX-139737909-T-C
• rs201858795
• NM_001353812.2:c.3288+7A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001353812.2(ATP11C):​c.3288+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,199,968 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 41 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.00013 (0 hom. 41 hem.)
• Consequence: ATP11C NM_001353812.2 splice_region, intron
• Scores: Splicing: ADA: 0.0004343
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.80
• Publications: 0 publications found

Genes affected

ATP11C (HGNC:13554): (ATPase phospholipid transporting 11C) Enables phosphatidylethanolamine flippase activity and phosphatidylserine flippase activity. Predicted to be involved in phospholipid translocation; positive regulation of B cell differentiation; and pre-B cell differentiation. Located in endoplasmic reticulum and plasma membrane. Is integral component of plasma membrane. Implicated in X-linked congenital hemolytic anemia. [provided by Alliance of Genome Resources, Apr 2022]

ATP11C Gene-Disease associations (from GenCC):

• X-linked congenital hemolytic anemia

  Inheritance: XL, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-139737909-T-C is Benign according to our data. Variant chrX-139737909-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3388892.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 41 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353812.2. 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
	ATP11C	NM_001353812.2	MANE Select	c.3288+7A>G		splice_region intron	N/A	NP_001340741.2	A0A804HIW2
	ATP11C	NM_173694.5		c.3297+7A>G		splice_region intron	N/A	NP_775965.3
	ATP11C	NM_001353811.2		c.3288+7A>G		splice_region intron	N/A	NP_001340740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP11C	ENST00000682941.1	MANE Select	c.3288+7A>G		splice_region intron	N/A	ENSP00000507250.1	A0A804HIW2
	ATP11C	ENST00000327569.7	TSL:1	c.3297+7A>G		splice_region intron	N/A	ENSP00000332756.3	Q8NB49-1
	ATP11C	ENST00000361648.6	TSL:1	c.3297+7A>G		splice_region intron	N/A	ENSP00000355165.2	Q8NB49-3

Frequencies

GnomAD3 genomes AF: 0.0000895 AC: 10 AN: 111771 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000814

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000755

Gnomad OTH AF: 0.000665

GnomAD2 exomes AF: 0.000115 AC: 20 AN: 174229 AF XY: 0.0000831

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000703

Gnomad NFE exome AF: 0.000102

Gnomad OTH exome AF: 0.000237

GnomAD4 exome AF: 0.000134 AC: 146 AN: 1088143 Hom.: 0 Cov.: 28 AF XY: 0.000115 AC XY: 41 AN XY: 355717

African (AFR) AF: 0.0000386 AC: 1 AN: 25927

American (AMR) AF: 0.00 AC: 0 AN: 34293

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18972

East Asian (EAS) AF: 0.00 AC: 0 AN: 30035

South Asian (SAS) AF: 0.00 AC: 0 AN: 52361

European-Finnish (FIN) AF: 0.000893 AC: 36 AN: 40330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4059

European-Non Finnish (NFE) AF: 0.000116 AC: 97 AN: 836584

Other (OTH) AF: 0.000263 AC: 12 AN: 45582

GnomAD4 genome AF: 0.0000894 AC: 10 AN: 111825 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34111

African (AFR) AF: 0.00 AC: 0 AN: 30883

American (AMR) AF: 0.00 AC: 0 AN: 10544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2645

East Asian (EAS) AF: 0.00 AC: 0 AN: 3519

South Asian (SAS) AF: 0.00 AC: 0 AN: 2680

European-Finnish (FIN) AF: 0.000814 AC: 5 AN: 6143

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000755 AC: 4 AN: 52984

Other (OTH) AF: 0.000657 AC: 1 AN: 1523

Alfa AF: 0.000108 Hom.: 0

Bravo AF: 0.0000453

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	-0.78
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00043
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.030		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: rs201858795; hg19: chrX-138820068;