22-17119915-C-G

Variant names:

• chr22-17119915-C-G
• NM_031890.4:c.1213G>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031890.4(TMEM121B):​c.1213G>C​(p.Asp405His) 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 pathogenic 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: 2.64

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM121B	NM_031890.4	c.1213G>C	p.Asp405His	missense_variant	Exon 1 of 1	ENST00000331437.4	NP_114096.1
TMEM121B	NM_001163079.2	c.148G>C	p.Asp50His	missense_variant	Exon 2 of 2		NP_001156551.1
TMEM121B	XM_011546124.3	c.1213G>C	p.Asp405His	missense_variant	Exon 1 of 2		XP_011544426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM121B	ENST00000331437.4	c.1213G>C	p.Asp405His	missense_variant	Exon 1 of 1	6	NM_031890.4	ENSP00000329318.3
TMEM121B	ENST00000399875.1	c.148G>C	p.Asp50His	missense_variant	Exon 2 of 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

Dec 07, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1213G>C (p.D405H) alteration is located in exon 1 (coding exon 1) of the CECR6 gene. This alteration results from a G to C substitution at nucleotide position 1213, causing the aspartic acid (D) at amino acid position 405 to be replaced by a histidine (H). 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	1.0
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.062
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.84	T;T
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.64	T
PrimateAI	Pathogenic	0.91	D
PROVEAN	Pathogenic	-6.6	D;D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.76
MutPred		0.54		.;Gain of helix (P = 0.0696);
MVP		0.42
ClinPred		0.99	D
GERP RS		3.3
Varity_R		0.85
gMVP		0.94

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: chr22-17600805;