Genetic Variant SPATA19:p.Arg161Lys (chr11-133842061-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_174927.3(SPATA19):c.482G>A(p.Arg161Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,064 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R161T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000025 ( 1 hom. )

Consequence

SPATA19
NM_174927.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.273

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 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=0.0640274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA19	NM_174927.3 link	c.482G>A	p.Arg161Lys	missense_variant	Exon 6 of 7	ENST00000299140.8	NP_777587.1	Q7Z5L4A0A140VKB6
SPATA19	NM_001291992.2 link	c.482G>A	p.Arg161Lys	missense_variant	Exon 6 of 7		NP_001278921.1	Q7Z5L4A0A140VKB6
SPATA19	XR_947806.2 link	n.549G>A		non_coding_transcript_exon_variant	Exon 6 of 8
SPATA19	XR_947807.2 link	n.549G>A		non_coding_transcript_exon_variant	Exon 6 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA19	ENST00000299140.8 link	c.482G>A	p.Arg161Lys	missense_variant	Exon 6 of 7	1	NM_174927.3	ENSP00000299140.3		Q7Z5L4
SPATA19	ENST00000532889.1 link	c.482G>A	p.Arg161Lys	missense_variant	Exon 6 of 7	5		ENSP00000435248.1		Q7Z5L4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

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

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000932

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 27, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482G>A (p.R161K) alteration is located in exon 6 (coding exon 6) of the SPATA19 gene. This alteration results from a G to A substitution at nucleotide position 482, causing the arginine (R) at amino acid position 161 to be replaced by a lysine (K). 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

0.088

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.0

DANN

Benign

0.88

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.29

.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.041

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.0040

B;B

Vest4

0.065

MutPred

0.16

Gain of ubiquitination at R161 (P = 0.0128);Gain of ubiquitination at R161 (P = 0.0128);

MVP

0.081

MPC

0.073

ClinPred

0.24

GERP RS

0.76

Varity_R

0.22

gMVP

0.031

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