Variant 1-244375383-C-T 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_001012970.3(C1orf100):c.68C>T(p.Ala23Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000943 in 1,613,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00099 ( 0 hom. )

Consequence

C1orf100
NM_001012970.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.822

Variant links:

Genes affected

C1orf100 (HGNC:):

C1orf100 links:

SPMIP3 (HGNC:30435): (sperm microtubule inner protein 3)

SPMIP3 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=0.022055268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1orf100	NM_001012970.3 linkuse as main transcript	c.68C>T	p.Ala23Val	missense_variant	3/5	ENST00000308105.5	NP_001012988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPMIP3	ENST00000308105.5 linkuse as main transcript	c.68C>T	p.Ala23Val	missense_variant	3/5	2	NM_001012970.3	ENSP00000311218	P1	Q5SVJ3-1
SPMIP3	ENST00000366537.5 linkuse as main transcript	c.68C>T	p.Ala23Val	missense_variant	3/5	1		ENSP00000355495		Q5SVJ3-2
	ENST00000417765.1 linkuse as main transcript	n.359G>A		non_coding_transcript_exon_variant	4/4	3
SPMIP3	ENST00000486803.1 linkuse as main transcript	n.167C>T		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.000999

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000454

AC:

114

AN:

251296

Hom.:

AF XY:

0.000486

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000933

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000990

AC:

1447

AN:

1461330

Hom.:

Cov.:

AF XY:

0.000975

AC XY:

709

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00126

Gnomad4 OTH exome

AF:

0.000580

GnomAD4 genome

AF:

0.000493

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000144

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:

0.000999

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000896

Hom.:

Bravo

AF:

0.000446

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000436

AC:

EpiCase

AF:

0.000764

EpiControl

AF:

0.000889

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

Nov 03, 2023

The c.68C>T (p.A23V) alteration is located in exon 3 (coding exon 2) of the C1orf100 gene. This alteration results from a C to T substitution at nucleotide position 68, causing the alanine (A) at amino acid position 23 to be replaced by a valine (V). 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

0.099

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.0

DANN

Benign

0.65

DEOGEN2

Benign

0.033

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0076

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.050

N;N

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.012

Sift

Benign

0.67

T;T

Sift4G

Benign

0.68

T;T

Polyphen

0.0

B;B

Vest4

0.14

MVP

0.014

MPC

0.045

ClinPred

0.0086

GERP RS

-6.1

Varity_R

0.052

gMVP

0.061

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