Variant chr1-162374076-A-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_182581.4(SPATA46):c.758T>C(p.Ile253Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,610,338 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 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SPATA46
NM_182581.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.15

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 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=0.030795217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA46	NM_182581.4 linkuse as main transcript	c.758T>C	p.Ile253Thr	missense_variant	3/3	ENST00000367935.10	NP_872387.2	Q5T0L3
SPATA46	XM_005245103.4 linkuse as main transcript	c.644T>C	p.Ile215Thr	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.758T>C	p.Ile253Thr	missense_variant	3/3	1	NM_182581.4	ENSP00000356912.4	Q5T0L3
ENSG00000254706	ENST00000420220.1 linkuse as main transcript	c.-12+6872A>G		intron_variant		5		ENSP00000398035.1	F8W6W0
ENSG00000254706	ENST00000431696.1 linkuse as main transcript	c.226+6872A>G		intron_variant		4		ENSP00000405676.2	H7C2G1
ENSG00000254706	ENST00000367932.3 linkuse as main transcript	n.152+6613A>G		intron_variant		4		ENSP00000356909.3	H7BY61

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000202

AC:

AN:

247720

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000148

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:

0.0000165

AC:

AN:

1458174

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

725150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

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:

0.0000189

ExAC

AF:

0.00000824

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 10, 2021

The c.758T>C (p.I253T) alteration is located in exon 3 (coding exon 3) of the C1orf111 gene. This alteration results from a T to C substitution at nucleotide position 758, causing the isoleucine (I) at amino acid position 253 to be replaced by a threonine (T). 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

0.056

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.0030

DANN

Benign

0.38

DEOGEN2

Benign

0.0084

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0054

LIST_S2

Benign

0.25

M_CAP

Benign

0.0032

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.97

PROVEAN

Benign

0.69

REVEL

Benign

0.040

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.035

MutPred

0.28

Loss of stability (P = 0.0118);

MVP

0.072

MPC

0.029

ClinPred

0.045

GERP RS

-9.7

Varity_R

0.048

gMVP

0.043

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