chr5-160565617-T-G

Variant names:

• chr5-160565617-T-G
• rs564583647
• NM_025153.3:c.4222A>C

Variant summary

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

The NM_025153.3(ATP10B):​c.4222A>C​(p.Met1408Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP10B NM_025153.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793
• Publications: 0 publications found

Genes affected

ATP10B (HGNC:13543): (ATPase phospholipid transporting 10B (putative)) Enables glycosylceramide flippase activity and phosphatidylcholine flippase activity. Involved in lysosomal membrane organization. Located in endoplasmic reticulum. Is integral component of lysosomal membrane. Part of phospholipid-translocating ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

MIR3142HG (HGNC:51944): (MIR3142 host gene)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0514355).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025153.3. 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
	ATP10B	NM_025153.3	MANE Select	c.4222A>C	p.Met1408Leu	missense	Exon 26 of 26	NP_079429.2	O94823-1
	ATP10B	NM_001366652.1		c.4222A>C	p.Met1408Leu	missense	Exon 25 of 25	NP_001353581.1	O94823-1
	ATP10B	NM_001366655.1		c.4222A>C	p.Met1408Leu	missense	Exon 25 of 25	NP_001353584.1	O94823-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP10B	ENST00000327245.10	TSL:1 MANE Select	c.4222A>C	p.Met1408Leu	missense	Exon 26 of 26	ENSP00000313600.5	O94823-1
	ATP10B	ENST00000943128.1		c.4222A>C	p.Met1408Leu	missense	Exon 26 of 26	ENSP00000613187.1
	ATP10B	ENST00000642502.1		c.4138A>C	p.Met1380Leu	missense	Exon 21 of 21	ENSP00000493802.1	A0A2R8YDI5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249066 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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 Cov.: 29

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.066
DANN	Benign	0.38
DEOGEN2	Benign	0.0014	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.79
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.061
Sift	Benign	0.37	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.20		Gain of catalytic residue at M1408 (P = 0.033)
MVP		0.26
MPC		0.073
ClinPred		0.025	T
GERP RS		-3.3
Varity_R		0.066
gMVP		0.12
Mutation Taster		=97/3	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: rs564583647; hg19: chr5-159992624;