chr8-132751885-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001382403.1(TMEM71):ā€‹c.214T>Cā€‹(p.Tyr72His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,022 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000053 ( 0 hom., cov: 32)
Exomes š‘“: 0.000020 ( 0 hom. )

Consequence

TMEM71
NM_001382403.1 missense

Scores

8
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.74
Variant links:
Genes affected
TMEM71 (HGNC:26572): (transmembrane protein 71) Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TMEM71NM_001382403.1 linkuse as main transcriptc.214T>C p.Tyr72His missense_variant 4/10 ENST00000677595.1 NP_001369332.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TMEM71ENST00000677595.1 linkuse as main transcriptc.214T>C p.Tyr72His missense_variant 4/10 NM_001382403.1 ENSP00000504388 P1Q6P5X7-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
251422
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000198
AC:
29
AN:
1461732
Hom.:
0
Cov.:
32
AF XY:
0.0000220
AC XY:
16
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000313
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152290
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00142
Bravo
AF:
0.0000982
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 16, 2023The c.214T>C (p.Y72H) alteration is located in exon 4 (coding exon 3) of the TMEM71 gene. This alteration results from a T to C substitution at nucleotide position 214, causing the tyrosine (Y) at amino acid position 72 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.39
CADD
Uncertain
25
DANN
Uncertain
1.0
Eigen
Pathogenic
0.83
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;D;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.58
D;D;D;D;D
MetaSVM
Uncertain
-0.057
T
MutationAssessor
Uncertain
2.3
.;M;M;.;.
MutationTaster
Benign
0.99
D;D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-4.8
D;D;D;D;D
REVEL
Uncertain
0.55
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;.
Polyphen
1.0
.;D;D;.;.
Vest4
0.95
MutPred
0.47
Gain of catalytic residue at Y72 (P = 0.0532);Gain of catalytic residue at Y72 (P = 0.0532);Gain of catalytic residue at Y72 (P = 0.0532);Gain of catalytic residue at Y72 (P = 0.0532);Gain of catalytic residue at Y72 (P = 0.0532);
MVP
0.12
MPC
0.32
ClinPred
0.62
D
GERP RS
5.8
gMVP
0.33

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs77624303; hg19: chr8-133764131; API