5-82312744-T-C

Variant names:

• chr5-82312744-T-C
• rs61740965
• ENST00000380167.8:n.1590T>C

Variant summary

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

The ENST00000380167.8(ATP6AP1L):​n.1590T>C variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00545 in 1,590,108 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (35 hom.)
• Consequence: ATP6AP1L ENST00000380167.8 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.77

Genes affected

ATP6AP1L (HGNC:28091): (ATPase H+ transporting accessory protein 1 like (pseudogene)) Predicted to be involved in regulation of cellular pH. Predicted to be integral component of membrane. Predicted to be part of plasma membrane proton-transporting V-type ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.02450344).
• BP6: Variant 5-82312744-T-C is Benign according to our data. Variant chr5-82312744-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2655574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1L	NR_169870.1	n.2235T>C		non_coding_transcript_exon_variant	Exon 11 of 12
ATP6AP1L	NR_172106.1	n.1829T>C		non_coding_transcript_exon_variant	Exon 9 of 10
ATP6AP1L	NR_172107.1	n.2329T>C		non_coding_transcript_exon_variant	Exon 10 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6AP1L	ENST00000380167.8	n.1590T>C		non_coding_transcript_exon_variant	Exon 9 of 10	2
ATP6AP1L	ENST00000508366.5	n.1483T>C		non_coding_transcript_exon_variant	Exon 2 of 8	2
ATP6AP1L	ENST00000514672.1	n.306T>C		non_coding_transcript_exon_variant	Exon 2 of 3	2
ATP6AP1L	ENST00000643922.1	n.617T>C		non_coding_transcript_exon_variant	Exon 6 of 7

Frequencies

GnomAD3 genomes AF: 0.00418 AC: 636 AN: 152208 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00570

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00660

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00382 AC: 870 AN: 227500 AF XY: 0.00370

Gnomad AFR exome AF: 0.00169

Gnomad AMR exome AF: 0.00478

Gnomad ASJ exome AF: 0.000215

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00388

Gnomad NFE exome AF: 0.00553

Gnomad OTH exome AF: 0.00681

GnomAD4 exome AF: 0.00559 AC: 8032 AN: 1437782 Hom.: 35 Cov.: 31 AF XY: 0.00534 AC XY: 3817 AN XY: 714622

Gnomad4 AFR exome AF: 0.000914 AC: 29 AN: 31718

Gnomad4 AMR exome AF: 0.00478 AC: 185 AN: 38674

Gnomad4 ASJ exome AF: 0.000118 AC: 3 AN: 25504

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 38358

Gnomad4 SAS exome AF: 0.000135 AC: 11 AN: 81754

Gnomad4 FIN exome AF: 0.00437 AC: 233 AN: 53268

Gnomad4 NFE exome AF: 0.00660 AC: 7284 AN: 1103330

Gnomad4 Remaining exome AF: 0.00472 AC: 281 AN: 59486

GnomAD4 genome AF: 0.00418 AC: 637 AN: 152326 Hom.: 1 Cov.: 33 AF XY: 0.00389 AC XY: 290 AN XY: 74488

Gnomad4 AFR AF: 0.00120 AC: 0.00120256 AN: 0.00120256

Gnomad4 AMR AF: 0.00569 AC: 0.00568776 AN: 0.00568776

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000414 AC: 0.000413907 AN: 0.000413907

Gnomad4 FIN AF: 0.00320 AC: 0.0032009 AN: 0.0032009

Gnomad4 NFE AF: 0.00661 AC: 0.00661492 AN: 0.00661492

Gnomad4 OTH AF: 0.00662 AC: 0.00662252 AN: 0.00662252

Alfa AF: 0.00507 Hom.: 8

Bravo AF: 0.00429

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00493 AC: 19

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00535 AC: 46

ExAC AF: 0.00383 AC: 465

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATP6AP1L: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Uncertain	0.050
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.025	T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.65
MVP		0.21
ClinPred		0.022	T
GERP RS		5.7
Varity_R		0.90
gMVP		0.83
Mutation Taster		=82/18	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

Publications

LitVar

Other links and lift over

dbSNP: rs61740965; hg19: chr5-81608563; COSMIC: COSV99061768;