22-21469339-C-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001388354.1(TMEM191C):​c.656C>A​(p.Ala219Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 13)
Exomes 𝑓: 0.0000020 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TMEM191C
NM_001388354.1 missense

Scores

2
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59
Variant links:
Genes affected
TMEM191C (HGNC:33601): (transmembrane protein 191C) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.30088073).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM191CNM_001388354.1 linkc.656C>A p.Ala219Glu missense_variant Exon 8 of 10 ENST00000536718.3 NP_001375283.1
TMEM191CNM_001207052.2 linkc.650C>A p.Ala217Glu missense_variant Exon 7 of 9 NP_001193981.2 A6NGB0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM191CENST00000536718.3 linkc.656C>A p.Ala219Glu missense_variant Exon 8 of 10 5 NM_001388354.1 ENSP00000490781.2 A0A1B0GW53

Frequencies

GnomAD3 genomes
Cov.:
13
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000203
AC:
2
AN:
984792
Hom.:
0
Cov.:
13
AF XY:
0.00000416
AC XY:
2
AN XY:
481014
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000409
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
13

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 29, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.791C>A (p.A264E) alteration is located in exon 7 (coding exon 7) of the TMEM191C gene. This alteration results from a C to A substitution at nucleotide position 791, causing the alanine (A) at amino acid position 264 to be replaced by a glutamic acid (E). 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
AlphaMissense
Uncertain
0.36
BayesDel_noAF
Benign
-0.68
CADD
Uncertain
24
DANN
Benign
0.94
DEOGEN2
Benign
0.042
T;.;.
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.52
T;.;.
MetaRNN
Benign
0.30
T;T;T
PrimateAI
Uncertain
0.76
T
GERP RS
2.0
Varity_R
0.25
gMVP
0.21

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-21823628; API