22-21467436-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001388354.1(TMEM191C):​c.-24C>T variant causes a 5 prime UTR 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: 5)

Consequence

TMEM191C
NM_001388354.1 5_prime_UTR

Scores

1
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.612
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.15203527).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM191CNM_001388354.1 linkc.-24C>T 5_prime_UTR_variant Exon 1 of 10 ENST00000536718.3 NP_001375283.1
TMEM191CNM_001207052.2 linkc.-24C>T 5_prime_UTR_variant Exon 1 of 9 NP_001193981.2 A6NGB0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM191CENST00000536718 linkc.-24C>T 5_prime_UTR_variant Exon 1 of 10 5 NM_001388354.1 ENSP00000490781.2 A0A1B0GW53

Frequencies

GnomAD3 genomes
Cov.:
5
GnomAD4 exome
Cov.:
3
GnomAD4 genome
Cov.:
5

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 27, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.118C>T (p.H40Y) alteration is located in exon 1 (coding exon 1) of the TMEM191C gene. This alteration results from a C to T substitution at nucleotide position 118, causing the histidine (H) at amino acid position 40 to be replaced by a tyrosine (Y). 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
Benign
0.11
BayesDel_noAF
Benign
-0.87
CADD
Benign
2.7
DANN
Benign
0.95
DEOGEN2
Benign
0.0090
T;.
FATHMM_MKL
Benign
0.0071
N
LIST_S2
Benign
0.49
T;.
MetaRNN
Benign
0.15
T;T
PrimateAI
Uncertain
0.64
T
GERP RS
-2.1
Varity_R
0.029
gMVP
0.019

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: chr22-21821725; API