22-18530001-C-A

Variant names:

• chr22-18530001-C-A
• NM_001242313.1:c.788C>A

Variant summary

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

The NM_001242313.1(TMEM191B):​c.788C>A​(p.Ala263Glu) 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: 0.0000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM191B NM_001242313.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.654

Genes affected

TMEM191B (HGNC:33600): (transmembrane protein 191B) 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=0.14748722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM191B	NM_001242313.1	c.788C>A	p.Ala263Glu	missense_variant	Exon 7 of 9	ENST00000612978.5	NP_001229242.1
TMEM191B	XM_011546160.4	c.794C>A	p.Ala265Glu	missense_variant	Exon 8 of 10		XP_011544462.1
TMEM191B	XR_951236.3	n.908C>A		non_coding_transcript_exon_variant	Exon 7 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM191B	ENST00000612978.5	c.788C>A	p.Ala263Glu	missense_variant	Exon 7 of 9	5	NM_001242313.1	ENSP00000481358.1

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000146 AC: 2 AN: 1372346 Hom.: 0 Cov.: 31 AF XY: 0.00000295 AC XY: 2 AN XY: 676842

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: 0.0000261

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.788C>A (p.A263E) alteration is located in exon 7 (coding exon 7) of the TMEM191B gene. This alteration results from a C to A substitution at nucleotide position 788, causing the alanine (A) at amino acid position 263 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	0.35
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.045	T;.
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.52	T;T
MetaRNN	Benign	0.15	T;T
PrimateAI	Uncertain	0.76	T
Sift4G	Benign	0.077	T;D
Vest4		0.17
MVP		0.25
GERP RS		1.1
Varity_R		0.095
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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: chr22-20379868;