rs201052330

Variant names:

• chrX-139741027-T-A
• rs201052330
• NM_001353812.2:c.3098A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-139741027-T-A
• chrX-139741027-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001353812.2(ATP11C):​c.3098A>T​(p.Tyr1033Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,204,641 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y1033C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 1 hem.)
• Consequence: ATP11C NM_001353812.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.63
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23248634).

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.3098A>T	p.Tyr1033Phe	missense	Exon 27 of 30	NP_001340741.2	A0A804HIW2
	ATP11C	NM_173694.5		c.3107A>T	p.Tyr1036Phe	missense	Exon 27 of 30	NP_775965.3
	ATP11C	NM_001353811.2		c.3098A>T	p.Tyr1033Phe	missense	Exon 27 of 30	NP_001340740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP11C	ENST00000682941.1	MANE Select	c.3098A>T	p.Tyr1033Phe	missense	Exon 27 of 30	ENSP00000507250.1	A0A804HIW2
	ATP11C	ENST00000327569.7	TSL:1	c.3107A>T	p.Tyr1036Phe	missense	Exon 27 of 30	ENSP00000332756.3	Q8NB49-1
	ATP11C	ENST00000361648.6	TSL:1	c.3107A>T	p.Tyr1036Phe	missense	Exon 27 of 29	ENSP00000355165.2	Q8NB49-3

Frequencies

GnomAD3 genomes AF: 0.00000897 AC: 1 AN: 111506 Hom.: 0 Cov.: 22

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: 0.000167

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000548 AC: 1 AN: 182376 AF XY: 0.00

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: 0.0000627

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1093081 Hom.: 0 Cov.: 27 AF XY: 0.00000278 AC XY: 1 AN XY: 359267

African (AFR) AF: 0.00 AC: 0 AN: 26241

American (AMR) AF: 0.00 AC: 0 AN: 35054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19297

East Asian (EAS) AF: 0.00 AC: 0 AN: 30162

South Asian (SAS) AF: 0.00 AC: 0 AN: 53971

European-Finnish (FIN) AF: 0.0000741 AC: 3 AN: 40487

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837889

Other (OTH) AF: 0.00 AC: 0 AN: 45866

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111560 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33828

African (AFR) AF: 0.00 AC: 0 AN: 30757

American (AMR) AF: 0.00 AC: 0 AN: 10494

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2634

East Asian (EAS) AF: 0.00 AC: 0 AN: 3518

South Asian (SAS) AF: 0.00 AC: 0 AN: 2650

European-Finnish (FIN) AF: 0.000167 AC: 1 AN: 6003

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53075

Other (OTH) AF: 0.00 AC: 0 AN: 1529

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.097	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.16
Sift	Benign	0.29	T
Sift4G	Benign	0.36	T
Polyphen		0.39	B
Vest4		0.52
MVP		0.42
MPC		1.3
ClinPred		0.61	D
GERP RS		5.5
Varity_R		0.78
gMVP		0.76
Mutation Taster		=56/44	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: rs201052330; hg19: chrX-138823186;