Variant 1-173635843-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000333279.3(ANKRD45):c.497-8684T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 1,525,536 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ANKRD45
ENST00000333279.3 intron

Scores

Splicing: ADA: 0.0002096

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

TEX50 (HGNC:52382): (testis expressed 50) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TEX50 links:

ANKRD45 (HGNC:24786): (ankyrin repeat domain 45)

ANKRD45 links:

ENSG00000285777 (HGNC:):

ENSG00000285777 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.24201915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX50	NM_001195190.3 linkuse as main transcript	c.322A>C	p.Lys108Gln	missense_variant, splice_region_variant	1/2	ENST00000417563.3	NP_001182119.1	A0A1B0GTY4
ANKRD45	NM_198493.3 linkuse as main transcript	c.497-8684T>G		intron_variant		ENST00000333279.3	NP_940895.1	Q5TZF3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEX50	ENST00000417563.3 linkuse as main transcript	c.322A>C	p.Lys108Gln	missense_variant, splice_region_variant	1/2	2	NM_001195190.3	ENSP00000489890.1	A0A1B0GTY4
ANKRD45	ENST00000333279.3 linkuse as main transcript	c.497-8684T>G		intron_variant		1	NM_198493.3	ENSP00000331268.2	Q5TZF3-2
ENSG00000285777	ENST00000648193.1 linkuse as main transcript	n.497-8684T>G		intron_variant				ENSP00000498204.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000308

AC:

AN:

129986

Hom.:

AF XY:

0.0000282

AC XY:

AN XY:

70968

show subpopulations

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:

0.000197

Gnomad NFE exome

AF:

0.0000589

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000218

AC:

AN:

1373406

Hom.:

Cov.:

AF XY:

0.0000148

AC XY:

AN XY:

677490

show subpopulations

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:

0.0000297

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Jul 13, 2021

The c.322A>C (p.K108Q) alteration is located in exon 1 (coding exon 1) of the LOC730159 gene. This alteration results from a A to C substitution at nucleotide position 322, causing the lysine (K) at amino acid position 108 to be replaced by a glutamine (Q). 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

0.15

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.63

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.46

MetaRNN

Benign

0.24

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

GERP RS

3.1

Varity_R

0.19

gMVP

0.034

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.0060

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