11-133842097-C-T

Variant names:

• chr11-133842097-C-T
• rs140608295
• NM_174927.3:c.446G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_174927.3(SPATA19):​c.446G>A​(p.Arg149His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: SPATA19 NM_174927.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.216

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022732735).
• BP6: Variant 11-133842097-C-T is Benign according to our data. Variant chr11-133842097-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3168233.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA19	NM_174927.3	c.446G>A	p.Arg149His	missense_variant	Exon 6 of 7	ENST00000299140.8	NP_777587.1
SPATA19	NM_001291992.2	c.446G>A	p.Arg149His	missense_variant	Exon 6 of 7		NP_001278921.1
SPATA19	XR_947806.2	n.513G>A		non_coding_transcript_exon_variant	Exon 6 of 8
SPATA19	XR_947807.2	n.513G>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	c.446G>A	p.Arg149His	missense_variant	Exon 6 of 7	1	NM_174927.3	ENSP00000299140.3
SPATA19	ENST00000532889.1	c.446G>A	p.Arg149His	missense_variant	Exon 6 of 7	5		ENSP00000435248.1

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000716 AC: 18 AN: 251296 Hom.: 0 AF XY: 0.0000884 AC XY: 12 AN XY: 135800

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000472 AC: 69 AN: 1461700 Hom.: 0 Cov.: 31 AF XY: 0.0000495 AC XY: 36 AN XY: 727128

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000405

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152344 Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26 AN XY: 74490

Gnomad4 AFR AF: 0.00115

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000350 Hom.: 0

Bravo AF: 0.000325

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Aug 09, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.2
DANN	Benign	0.81
DEOGEN2	Benign	0.0044	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00048	N
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.023	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.0	N;N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	1.8	N;N
REVEL	Benign	0.030
Sift	Benign	0.96	T;T
Sift4G	Benign	0.88	T;T
Polyphen		0.0010	B;B
Vest4		0.071
MVP		0.10
MPC		0.061
ClinPred		0.0075	T
GERP RS		3.2
Varity_R		0.015
gMVP		0.012

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs140608295; hg19: chr11-133711992; COSMIC: COSV54483094;