Genetic Variant SPACA4:p.Thr49Ile (chr19-48607124-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_133498.3(SPACA4):c.146C>T(p.Thr49Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,612,978 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict 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: 0.000023 ( 1 hom. )

Consequence

SPACA4
NM_133498.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.653

Publications

0 publications found

Variant links:

Genes affected

SPACA4 (HGNC:16441): (sperm acrosome associated 4) Predicted to be involved in cell adhesion. Predicted to be located in extracellular region and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPACA4 links:

FAM83E (HGNC:25972): (family with sequence similarity 83 member E) Enables protein kinase binding activity. Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

FAM83E links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026692271).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133498.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPACA4	NM_133498.3	MANE Select	c.146C>T	p.Thr49Ile	missense	Exon 1 of 1	NP_598005.1	Q8TDM5
	FAM83E	NM_017708.4	MANE Select	c.758+2752G>A		intron	N/A	NP_060178.2	Q2M2I3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SPACA4	ENST00000321762.3	TSL:6 MANE Select	c.146C>T	p.Thr49Ile	missense	Exon 1 of 1	ENSP00000312774.1	Q8TDM5
FAM83E	ENST00000263266.4	TSL:1 MANE Select	c.758+2752G>A		intron	N/A	ENSP00000263266.2	Q2M2I3
FAM83E	ENST00000876133.1		c.758+2752G>A		intron	N/A	ENSP00000546192.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD2 exomes

AF:

0.000108

AC:

AN:

250320

AF XY:

0.0000812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000233

AC:

AN:

1460738

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726768

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.000760

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111974

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41466

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000357

Hom.:

Bravo

AF:

0.0000264

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000988

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.44

CADD

Benign

2.3

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.050

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.43

M_CAP

Benign

0.018

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.6

PhyloP100

-0.65

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.049

Sift

Benign

0.11

Sift4G

Uncertain

0.024

Polyphen

0.16

Vest4

0.060

MutPred

0.50

Gain of sheet (P = 0.0344)

MVP

0.19

MPC

0.79

ClinPred

0.048

GERP RS

0.44

PromoterAI

0.00090

Neutral

(source)

Varity_R

0.064

gMVP

0.68

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over