Variant 1-162374359-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182581.4(SPATA46):c.475C>T(p.His159Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SPATA46
NM_182581.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

Variant links:

Genes affected

SPATA46 (HGNC:27648): (spermatogenesis associated 46) Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization and spermatogenesis. Predicted to be active in nuclear membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA46 links:

ENSG00000254706 (HGNC:):

ENSG00000254706 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=0.15258753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA46	NM_182581.4 linkuse as main transcript	c.475C>T	p.His159Tyr	missense_variant	3/3	ENST00000367935.10	NP_872387.2	Q5T0L3
SPATA46	XM_005245103.4 linkuse as main transcript	c.361C>T	p.His121Tyr	missense_variant	2/2		XP_005245160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPATA46	ENST00000367935.10 linkuse as main transcript	c.475C>T	p.His159Tyr	missense_variant	3/3	1	NM_182581.4	ENSP00000356912.4	Q5T0L3
ENSG00000254706	ENST00000420220.1 linkuse as main transcript	c.-12+7155G>A		intron_variant		5		ENSP00000398035.1	F8W6W0
ENSG00000254706	ENST00000431696.1 linkuse as main transcript	c.226+7155G>A		intron_variant		4		ENSP00000405676.2	H7C2G1
ENSG00000254706	ENST00000367932.3 linkuse as main transcript	n.152+6896G>A		intron_variant		4		ENSP00000356909.3	H7BY61

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251482

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135914

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 12, 2021

The c.475C>T (p.H159Y) alteration is located in exon 3 (coding exon 3) of the C1orf111 gene. This alteration results from a C to T substitution at nucleotide position 475, causing the histidine (H) at amino acid position 159 to be replaced by a tyrosine (Y). 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

0.093

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.020

Eigen

Benign

-0.068

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.62

M_CAP

Benign

0.0087

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

PROVEAN

Benign

-1.7

REVEL

Benign

0.054

Sift

Benign

0.053

Sift4G

Uncertain

0.059

Polyphen

0.96

Vest4

0.24

MutPred

0.21

Loss of methylation at K156 (P = 0.0721);

MVP

0.22

MPC

0.14

ClinPred

0.43

GERP RS

4.3

Varity_R

0.057

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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