22-37001943-T-G

Position:

• chr22-37001943-T-G

Variant summary

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

The NM_001163857.2(TEX33):​c.383A>C​(p.Gln128Pro) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TEX33 NM_001163857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.876

Genes affected

TEX33 (HGNC:):

CIMIP4 (HGNC:28568): (ciliary microtubule inner protein 4)

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=0.084091276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX33	NM_001163857.2	c.383A>C	p.Gln128Pro	missense_variant	3/6	ENST00000381821.2	NP_001157329.1
TEX33	NM_178552.4	c.128A>C	p.Gln43Pro	missense_variant	3/6		NP_848647.1
TEX33	XM_011530165.3	c.383A>C	p.Gln128Pro	missense_variant	4/7		XP_011528467.1
TEX33	XM_011530166.2	c.128A>C	p.Gln43Pro	missense_variant	3/6		XP_011528468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIMIP4	ENST00000381821.2	c.383A>C	p.Gln128Pro	missense_variant	3/6	1	NM_001163857.2	ENSP00000371243	P2
CIMIP4	ENST00000402860.7	c.128A>C	p.Gln43Pro	missense_variant	3/6	1		ENSP00000385179	A2
CIMIP4	ENST00000405091.6	c.383A>C	p.Gln128Pro	missense_variant	4/7	5		ENSP00000386118	P2
CIMIP4	ENST00000442538.5	c.64+250A>C		intron_variant		3		ENSP00000406640

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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

Apr 09, 2024

The c.383A>C (p.Q128P) alteration is located in exon 3 (coding exon 2) of the TEX33 gene. This alteration results from a A to C substitution at nucleotide position 383, causing the glutamine (Q) at amino acid position 128 to be replaced by a proline (P). 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	0.085
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0039	.;T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.46	T;.;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.084	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	.;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.30	T;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.011	.;B;B
Vest4		0.20
MutPred		0.076		.;Gain of glycosylation at T133 (P = 0.0853);Gain of glycosylation at T133 (P = 0.0853);
MVP		0.014
MPC		0.066
ClinPred		0.11	T
GERP RS		2.7
Varity_R		0.21
gMVP		0.092

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: chr22-37397984;