chr22-17119461-T-C

Position:

• chr22-17119461-T-C

Variant summary

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

The NM_031890.4(TMEM121B):​c.1667A>G​(p.His556Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• 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: 5.16

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.1667A>G	p.His556Arg	missense_variant	1/1	ENST00000331437.4	NP_114096.1
TMEM121B	NM_001163079.2	c.602A>G	p.His201Arg	missense_variant	2/2		NP_001156551.1
TMEM121B	XM_011546124.3	c.1667A>G	p.His556Arg	missense_variant	1/2		XP_011544426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM121B	ENST00000331437.4	c.1667A>G	p.His556Arg	missense_variant	1/1	6	NM_031890.4	ENSP00000329318.3
TMEM121B	ENST00000399875.1	c.602A>G	p.His201Arg	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: 1453902 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 722692

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 26, 2023

The c.1667A>G (p.H556R) alteration is located in exon 1 (coding exon 1) of the CECR6 gene. This alteration results from a A to G substitution at nucleotide position 1667, causing the histidine (H) at amino acid position 556 to be replaced by an arginine (R). 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	0.38
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.47	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.55	T
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-6.2	D;D
REVEL	Uncertain	0.41
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.59
MutPred		0.42		.;Gain of phosphorylation at S559 (P = 0.0716);
MVP		0.25
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.83
gMVP		0.85

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: chr22-17600351;