22-21469339-C-A

Variant names:

• chr22-21469339-C-A
• NM_001388354.1:c.656C>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

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 -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
TMEM191C	NM_001388354.1	c.656C>A	p.Ala219Glu	missense_variant	Exon 8 of 10	ENST00000536718.3	NP_001375283.1
TMEM191C	NM_001207052.2	c.650C>A	p.Ala217Glu	missense_variant	Exon 7 of 9		NP_001193981.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM191C	ENST00000536718.3	c.656C>A	p.Ala219Glu	missense_variant	Exon 8 of 10	5	NM_001388354.1	ENSP00000490781.2

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

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

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;