11-111534428-T-C

Position:

• chr11-111534428-T-C

Variant summary

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

The NM_001100388.2(HOATZ):​c.416T>C​(p.Leu139Pro) 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. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HOATZ NM_001100388.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0670

Genes affected

HOATZ (HGNC:25061): (HOATZ cilia and flagella associated protein) Predicted to be involved in axoneme assembly; flagellated sperm motility; and spermatogenesis. Predicted to be located in cilium and cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.11990839).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOATZ	NM_001100388.2	c.416T>C	p.Leu139Pro	missense_variant	5/6	ENST00000375618.9	NP_001093858.1
HOATZ	NM_207430.2	c.497T>C	p.Leu166Pro	missense_variant	6/7		NP_997313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOATZ	ENST00000375618.9	c.416T>C	p.Leu139Pro	missense_variant	5/6	1	NM_001100388.2	ENSP00000364768	P1
HOATZ	ENST00000332814.6	c.497T>C	p.Leu166Pro	missense_variant	6/7	5		ENSP00000333845
HOATZ	ENST00000529167.5	c.497T>C	p.Leu166Pro	missense_variant	6/6	2		ENSP00000432911
HOATZ	ENST00000529661.1	c.*236T>C		3_prime_UTR_variant, NMD_transcript_variant	4/5	3		ENSP00000435029

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

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, 2021

The c.497T>C (p.L166P) alteration is located in exon 6 (coding exon 6) of the C11orf88 gene. This alteration results from a T to C substitution at nucleotide position 497, causing the leucine (L) at amino acid position 166 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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;.;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.62	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	1.8	L;.;.
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.016	D;D;D
Sift4G	Uncertain	0.038	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.30
MutPred		0.20		Gain of glycosylation at L139 (P = 0.0183);.;.;
MVP		0.19
MPC		0.88
ClinPred		0.64	D
GERP RS		1.2
Varity_R		0.24
gMVP		0.024

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: chr11-111405153;