22-37001860-C-T

Variant names:

• chr22-37001860-C-T
• rs1446586576
• NM_001163857.2:c.466G>A

Variant summary

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

The NM_001163857.2(CIMIP4):​c.466G>A​(p.Asp156Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,449,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: CIMIP4 NM_001163857.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

Genes affected

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=0.23845086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIMIP4	NM_001163857.2	c.466G>A	p.Asp156Asn	missense_variant	Exon 3 of 6	ENST00000381821.2	NP_001157329.1
CIMIP4	NM_178552.4	c.211G>A	p.Asp71Asn	missense_variant	Exon 3 of 6		NP_848647.1
CIMIP4	XM_011530165.3	c.466G>A	p.Asp156Asn	missense_variant	Exon 4 of 7		XP_011528467.1
CIMIP4	XM_011530166.2	c.211G>A	p.Asp71Asn	missense_variant	Exon 3 of 6		XP_011528468.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX33	ENST00000381821.2	c.466G>A	p.Asp156Asn	missense_variant	Exon 3 of 6	1	NM_001163857.2	ENSP00000371243.1
TEX33	ENST00000402860.7	c.211G>A	p.Asp71Asn	missense_variant	Exon 3 of 6	1		ENSP00000385179.3
TEX33	ENST00000405091.6	c.466G>A	p.Asp156Asn	missense_variant	Exon 4 of 7	5		ENSP00000386118.2
TEX33	ENST00000442538.5	c.63+333G>A		intron_variant	Intron 1 of 3	3		ENSP00000406640.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000835 AC: 2 AN: 239602 Hom.: 0 AF XY: 0.0000155 AC XY: 2 AN XY: 129084

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000185

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000276 AC: 4 AN: 1449232 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 719456

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: 0.00000362

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 15, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.466G>A (p.D156N) alteration is located in exon 3 (coding exon 2) of the TEX33 gene. This alteration results from a G to A substitution at nucleotide position 466, causing the aspartic acid (D) at amino acid position 156 to be replaced by an asparagine (N). 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	0.18
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.074	.;T;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.70	T;.;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.6	.;M;M
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Uncertain	0.32
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		0.89	.;P;P
Vest4		0.23
MutPred		0.31		.;Gain of MoRF binding (P = 0.0451);Gain of MoRF binding (P = 0.0451);
MVP		0.061
MPC		0.15
ClinPred		0.93	D
GERP RS		3.0
Varity_R		0.23
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1446586576; hg19: chr22-37397901;