22-18528036-G-A

Variant names:

• chr22-18528036-G-A
• NM_001242313.1:c.56G>A

Variant summary

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

The NM_001242313.1(TMEM191B):​c.56G>A​(p.Arg19Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 2)
• Consequence: TMEM191B NM_001242313.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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=0.120385915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM191B	NM_001242313.1	c.56G>A	p.Arg19Lys	missense_variant	Exon 1 of 9	ENST00000612978.5	NP_001229242.1
TMEM191B	XM_011546160.4	c.56G>A	p.Arg19Lys	missense_variant	Exon 1 of 10		XP_011544462.1
TMEM191B	XR_951236.3	n.235G>A		non_coding_transcript_exon_variant	Exon 1 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM191B	ENST00000612978.5	c.56G>A	p.Arg19Lys	missense_variant	Exon 1 of 9	5	NM_001242313.1	ENSP00000481358.1
TMEM191B	ENST00000613577.5	c.56G>A	p.Arg19Lys	missense_variant	Exon 1 of 10	3		ENSP00000483146.2
TMEM191B	ENST00000614395.4	n.235G>A		non_coding_transcript_exon_variant	Exon 1 of 5	2

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD4 exome Cov.: 3

GnomAD4 genome Cov.: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 20, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.56G>A (p.R19K) alteration is located in exon 1 (coding exon 1) of the TMEM191B gene. This alteration results from a G to A substitution at nucleotide position 56, causing the arginine (R) at amino acid position 19 to be replaced by a lysine (K). 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	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.0
DANN	Benign	0.97
DEOGEN2	Benign	0.0065	T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.40	T
MetaRNN	Benign	0.12	T
PrimateAI	Uncertain	0.62	T
Sift4G	Pathogenic	0.0	D
Vest4		0.10
MVP		0.076
Varity_R		0.21
gMVP		0.040

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr22-20377903;