Variant 11-111514929-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100388.2(HOATZ):c.145C>G(p.Pro49Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

HOATZ
NM_001100388.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0350

Variant links:

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]

HOATZ links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05362484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOATZ	NM_001100388.2 linkuse as main transcript	c.145C>G	p.Pro49Ala	missense_variant	1/6	ENST00000375618.9	NP_001093858.1
HOATZ	NM_207430.2 linkuse as main transcript	c.145C>G	p.Pro49Ala	missense_variant	1/7		NP_997313.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOATZ	ENST00000375618.9 linkuse as main transcript	c.145C>G	p.Pro49Ala	missense_variant	1/6	1	NM_001100388.2	ENSP00000364768	P1	Q6PI97-1
	ENST00000530283.1 linkuse as main transcript	n.269G>C		non_coding_transcript_exon_variant	2/2	1
HOATZ	ENST00000332814.6 linkuse as main transcript	c.145C>G	p.Pro49Ala	missense_variant	1/7	5		ENSP00000333845		Q6PI97-3
HOATZ	ENST00000529167.5 linkuse as main transcript	c.145C>G	p.Pro49Ala	missense_variant	1/6	2		ENSP00000432911

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000281

AC:

AN:

249450

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.000116

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.0000894

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000125

AC:

AN:

152066

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000155

ESP6500AA

AF:

0.000475

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000413

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2021

The c.145C>G (p.P49A) alteration is located in exon 1 (coding exon 1) of the C11orf88 gene. This alteration results from a C to G substitution at nucleotide position 145, causing the proline (P) at amino acid position 49 to be replaced by an alanine (A). 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

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.10

T;.;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.054

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;L

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Pathogenic

-5.4

D;D;D

REVEL

Benign

0.073

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.21

B;.;.

Vest4

0.26

MVP

0.072

MPC

0.29

ClinPred

0.099

GERP RS

-0.58

Varity_R

0.079

gMVP

0.072

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over