Genetic Variant SPATA19:p.Arg123His (chr11-133842554-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_174927.3(SPATA19):c.368G>A(p.Arg123His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,580 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 1 hom. )

Consequence

SPATA19
NM_174927.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

SPATA19 (HGNC:30614): (spermatogenesis associated 19) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be located in mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA19 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=0.16412088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA19	NM_174927.3 link	c.368G>A	p.Arg123His	missense_variant	Exon 5 of 7	ENST00000299140.8	NP_777587.1	Q7Z5L4A0A140VKB6
SPATA19	NM_001291992.2 link	c.368G>A	p.Arg123His	missense_variant	Exon 5 of 7		NP_001278921.1	Q7Z5L4A0A140VKB6
SPATA19	XR_947806.2 link	n.435G>A		non_coding_transcript_exon_variant	Exon 5 of 8
SPATA19	XR_947807.2 link	n.435G>A		non_coding_transcript_exon_variant	Exon 5 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA19	ENST00000299140.8 link	c.368G>A	p.Arg123His	missense_variant	Exon 5 of 7	1	NM_174927.3	ENSP00000299140.3		Q7Z5L4
SPATA19	ENST00000532889.1 link	c.368G>A	p.Arg123His	missense_variant	Exon 5 of 7	5		ENSP00000435248.1		Q7Z5L4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251484

Hom.:

AF XY:

0.0000589

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:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1461500

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.368G>A (p.R123H) alteration is located in exon 5 (coding exon 5) of the SPATA19 gene. This alteration results from a G to A substitution at nucleotide position 368, causing the arginine (R) at amino acid position 123 to be replaced by a histidine (H). 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

Uncertain

0.35

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

0.018

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.5

L;L

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-4.4

D;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.15

T;T

Polyphen

0.53

P;P

Vest4

0.45

MutPred

0.42

Loss of MoRF binding (P = 0.0214);Loss of MoRF binding (P = 0.0214);

MVP

0.37

MPC

0.34

ClinPred

0.78

GERP RS

4.7

Varity_R

0.53

gMVP

0.060

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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