GeneBe

rs71269968

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The ENST00000520167.5(TMEM70):​n.317+89_317+154delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 226,224 control chromosomes in the GnomAD database, including 54 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0034 ( 54 hom. )

Consequence

TMEM70
ENST00000520167.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.351

Publications

1 publications found
Variant links:
Genes affected
TMEM70 (HGNC:26050): (transmembrane protein 70) This gene likely encodes a mitochondrial membrane protein. The encoded protein may play a role in biogenesis of mitochondrial ATP synthase. Mutations in this gene have been associated with neonatal mitochondrial encephalocardiomyopathy due to ATP synthase deficiency. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
TMEM70 Gene-Disease associations (from GenCC):
  • mitochondrial complex V (ATP synthase) deficiency, nuclear type 2
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet
  • mitochondrial disease
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1
Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0021 (217/103488) while in subpopulation AMR AF = 0.0041 (46/11230). AF 95% confidence interval is 0.00316. There are 0 homozygotes in GnomAd4. There are 113 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 54 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520167.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TMEM70
NM_017866.6
MANE Select
c.-232_-167delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG
upstream_gene
N/ANP_060336.3
TMEM70
NM_001040613.3
c.-232_-167delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG
upstream_gene
N/ANP_001035703.1Q9BUB7-3
TMEM70
NR_033334.2
n.-145_-80delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG
upstream_gene
N/A

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
TMEM70
ENST00000520167.5
TSL:2
n.317+89_317+154delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG
intron
N/A
TMEM70
ENST00000523794.1
TSL:3
n.574+89_574+154delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG
intron
N/A
TMEM70
ENST00000312184.6
TSL:1 MANE Select
c.-232_-167delGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCGGGCGGCAGGCG
upstream_gene
N/AENSP00000312599.5Q9BUB7-1

Frequencies

GnomAD3 genomes
AF:
0.00210
AC:
217
AN:
103400
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00356
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00410
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000331
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00121
Gnomad OTH
AF:
0.00293
GnomAD4 exome
AF:
0.00341
AC:
419
AN:
122736
Hom.:
54
AF XY:
0.00315
AC XY:
207
AN XY:
65692
show subpopulations
African (AFR)
AF:
0.00490
AC:
24
AN:
4898
American (AMR)
AF:
0.00880
AC:
82
AN:
9322
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
6046
East Asian (EAS)
AF:
0.000174
AC:
1
AN:
5732
South Asian (SAS)
AF:
0.00105
AC:
16
AN:
15264
European-Finnish (FIN)
AF:
0.000302
AC:
2
AN:
6612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
748
European-Non Finnish (NFE)
AF:
0.00382
AC:
253
AN:
66180
Other (OTH)
AF:
0.00517
AC:
41
AN:
7934
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.705
Heterozygous variant carriers
0
9
18
26
35
44
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00210
AC:
217
AN:
103488
Hom.:
0
Cov.:
0
AF XY:
0.00225
AC XY:
113
AN XY:
50260
show subpopulations
African (AFR)
AF:
0.00355
AC:
113
AN:
31816
American (AMR)
AF:
0.00410
AC:
46
AN:
11230
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2770
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3014
South Asian (SAS)
AF:
0.000331
AC:
1
AN:
3020
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
5666
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
220
European-Non Finnish (NFE)
AF:
0.00121
AC:
53
AN:
43820
Other (OTH)
AF:
0.00290
AC:
4
AN:
1380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
8
16
23
31
39
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs71269968; hg19: chr8-74888284; API