chr22-17119837-C-A

Position:

• chr22-17119837-C-A

Variant summary

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

The NM_031890.4(TMEM121B):​c.1291G>T​(p.Val431Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM121B NM_031890.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.52

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM121B	NM_031890.4	c.1291G>T	p.Val431Phe	missense_variant	1/1	ENST00000331437.4	NP_114096.1
TMEM121B	NM_001163079.2	c.226G>T	p.Val76Phe	missense_variant	2/2		NP_001156551.1
TMEM121B	XM_011546124.3	c.1291G>T	p.Val431Phe	missense_variant	1/2		XP_011544426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM121B	ENST00000331437.4	c.1291G>T	p.Val431Phe	missense_variant	1/1	6	NM_031890.4	ENSP00000329318.3
TMEM121B	ENST00000399875.1	c.226G>T	p.Val76Phe	missense_variant	2/2	2		ENSP00000382764.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1435100 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 713212

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Sep 01, 2024

The c.1291G>T (p.V431F) 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 1291, causing the valine (V) at amino acid position 431 to be replaced by a phenylalanine (F). 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	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	.;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.65	T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.71	T
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-2.9	D;N
REVEL	Benign	0.24
Sift	Pathogenic	0.0	D;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.55
MutPred		0.40		.;Loss of stability (P = 0.1182);
MVP		0.32
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.32
gMVP		0.69

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: chr22-17600727;