22-17119962-C-A

Position:

• chr22-17119962-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031890.4(TMEM121B):​c.1166G>T​(p.Arg389Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TMEM121B NM_031890.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

Genes affected

TMEM121B (HGNC:1844): (transmembrane protein 121B)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14322537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM121B	NM_031890.4	c.1166G>T	p.Arg389Leu	missense_variant	1/1	ENST00000331437.4	NP_114096.1
TMEM121B	NM_001163079.2	c.101G>T	p.Arg34Leu	missense_variant	2/2		NP_001156551.1
TMEM121B	XM_011546124.3	c.1166G>T	p.Arg389Leu	missense_variant	1/2		XP_011544426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM121B	ENST00000331437.4	c.1166G>T	p.Arg389Leu	missense_variant	1/1	6	NM_031890.4	ENSP00000329318.3
TMEM121B	ENST00000399875.1	c.101G>T	p.Arg34Leu	missense_variant	2/2	2		ENSP00000382764.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.1166G>T (p.R389L) alteration is located in exon 1 (coding exon 1) of the CECR6 gene. This alteration results from a G to T substitution at nucleotide position 1166, causing the arginine (R) at amino acid position 389 to be replaced by a leucine (L). 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	0.16
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	.;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.4	D;D
REVEL	Benign	0.037
Sift	Benign	0.070	T;T
Sift4G	Benign	0.13	T;D
Polyphen		0.14	.;B
Vest4		0.21
MutPred		0.32		.;Loss of disorder (P = 0.0592);
MVP		0.27
ClinPred		0.28	T
GERP RS		0.60
Varity_R		0.14
gMVP		0.68

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: chr22-17600852;