7-138706551-G-A

Variant names:

• chr7-138706551-G-A
• rs78419825
• NM_020632.3:c.*73C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_020632.3(ATP6V0A4):​c.*73C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,562,486 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (49 hom.)
• Consequence: ATP6V0A4 NM_020632.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.125
• Publications: 1 publications found

Genes affected

ATP6V0A4 (HGNC:866): (ATPase H+ transporting V0 subunit a4) This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. This gene is one of four genes in man and mouse that encode different isoforms of the a subunit. Alternatively spliced transcript variants encoding the same protein have been described. Mutations in this gene are associated with renal tubular acidosis associated with preserved hearing. [provided by RefSeq, Jul 2008]

ATP6V0A4 Gene-Disease associations (from GenCC):

• renal tubular acidosis, distal, 3, with or without sensorineural hearing loss

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal recessive distal renal tubular acidosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-138706551-G-A is Benign according to our data. Variant chr7-138706551-G-A is described in ClinVar as Benign. ClinVar VariationId is 359002.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00411 (625/152174) while in subpopulation SAS AF = 0.027 (130/4818). AF 95% confidence interval is 0.0232. There are 7 homozygotes in GnomAd4. There are 309 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020632.3. 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
	ATP6V0A4	NM_020632.3	MANE Select	c.*73C>T		3_prime_UTR	Exon 22 of 22	NP_065683.2	Q9HBG4
	ATP6V0A4	NM_130840.3		c.*73C>T		3_prime_UTR	Exon 21 of 21	NP_570855.2	Q9HBG4
	ATP6V0A4	NM_130841.3		c.*73C>T		3_prime_UTR	Exon 21 of 21	NP_570856.2	Q9HBG4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6V0A4	ENST00000310018.7	TSL:1 MANE Select	c.*73C>T		3_prime_UTR	Exon 22 of 22	ENSP00000308122.2	Q9HBG4
	ATP6V0A4	ENST00000353492.4	TSL:1	c.*73C>T		3_prime_UTR	Exon 21 of 21	ENSP00000253856.6	Q9HBG4
	ATP6V0A4	ENST00000393054.5	TSL:5	c.*73C>T		3_prime_UTR	Exon 21 of 21	ENSP00000376774.1	Q9HBG4

Frequencies

GnomAD3 genomes AF: 0.00410 AC: 623 AN: 152056 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000959

GnomAD4 exome AF: 0.00180 AC: 2534 AN: 1410312 Hom.: 49 Cov.: 26 AF XY: 0.00236 AC XY: 1663 AN XY: 704018

African (AFR) AF: 0.0109 AC: 353 AN: 32332

American (AMR) AF: 0.000822 AC: 36 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.000273 AC: 7 AN: 25614

East Asian (EAS) AF: 0.0000765 AC: 3 AN: 39226

South Asian (SAS) AF: 0.0230 AC: 1945 AN: 84632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51024

Middle Eastern (MID) AF: 0.00285 AC: 16 AN: 5620

European-Non Finnish (NFE) AF: 0.0000215 AC: 23 AN: 1069480

Other (OTH) AF: 0.00258 AC: 151 AN: 58614

GnomAD4 genome AF: 0.00411 AC: 625 AN: 152174 Hom.: 7 Cov.: 31 AF XY: 0.00415 AC XY: 309 AN XY: 74406

African (AFR) AF: 0.0115 AC: 478 AN: 41520

American (AMR) AF: 0.000851 AC: 13 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.0270 AC: 130 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68010

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00155 Hom.: 0

Bravo AF: 0.00375

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive distal renal tubular acidosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.65
DANN	Benign	0.57
PhyloP100		0.13
Mutation Taster		=100/0	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: rs78419825; hg19: chr7-138391296;