chr22-21469339-C-A

Variant names:

• chr22-21469339-C-A
• NM_001388354.1:c.656C>A

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388354.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM191C	NM_001388354.1	MANE Select	c.656C>A	p.Ala219Glu	missense	Exon 8 of 10	NP_001375283.1	A6NGB0-2
	TMEM191C	NM_001207052.2		c.650C>A	p.Ala217Glu	missense	Exon 7 of 9	NP_001193981.2	A6NGB0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM191C	ENST00000536718.3	TSL:5 MANE Select	c.656C>A	p.Ala219Glu	missense	Exon 8 of 10	ENSP00000490781.2	A6NGB0-2
	TMEM191C	ENST00000432134.8	TSL:5	c.680C>A	p.Ala227Glu	missense	Exon 8 of 10	ENSP00000490383.3	A0A1B0GV61
	TMEM191C	ENST00000621561.5	TSL:5	c.650C>A	p.Ala217Glu	missense	Exon 7 of 9	ENSP00000489706.2	A6NGB0-1

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

African (AFR) AF: 0.00 AC: 0 AN: 19072

American (AMR) AF: 0.00 AC: 0 AN: 9920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14472

East Asian (EAS) AF: 0.00 AC: 0 AN: 26912

South Asian (SAS) AF: 0.0000409 AC: 2 AN: 48876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2822

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 793356

Other (OTH) AF: 0.00 AC: 0 AN: 41962

GnomAD4 genome Cov.: 13

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.6
PrimateAI	Uncertain	0.76	T
GERP RS		2.0
Varity_R		0.25
gMVP		0.21
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

hg19: chr22-21823628;