22-21467436-C-T

Variant names:

• chr22-21467436-C-T
• NM_001388354.1:c.-24C>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.612

Genes affected

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

ACMG classification

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
TMEM191C	NM_001388354.1	c.-24C>T		5_prime_UTR_variant	Exon 1 of 10	ENST00000536718.3	NP_001375283.1
TMEM191C	NM_001207052.2	c.-24C>T		5_prime_UTR_variant	Exon 1 of 9		NP_001193981.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM191C	ENST00000536718	c.-24C>T		5_prime_UTR_variant	Exon 1 of 10	5	NM_001388354.1	ENSP00000490781.2

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

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;