chr11-133842061-C-G

Variant names:

• chr11-133842061-C-G
• rs146859197
• NM_174927.3:c.482G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174927.3(SPATA19):​c.482G>C​(p.Arg161Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 152,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. R161K) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000039 (0 hom., cov: 33)
• Consequence: SPATA19 NM_174927.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.273
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078413755).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174927.3. 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
	SPATA19	NM_174927.3	MANE Select	c.482G>C	p.Arg161Thr	missense	Exon 6 of 7	NP_777587.1	A0A140VKB6
	SPATA19	NM_001291992.2		c.482G>C	p.Arg161Thr	missense	Exon 6 of 7	NP_001278921.1	A0A140VKB6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA19	ENST00000299140.8	TSL:1 MANE Select	c.482G>C	p.Arg161Thr	missense	Exon 6 of 7	ENSP00000299140.3	Q7Z5L4
	SPATA19	ENST00000532889.1	TSL:5	c.482G>C	p.Arg161Thr	missense	Exon 6 of 7	ENSP00000435248.1	Q7Z5L4

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152264 Hom.: 0 Cov.: 33

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251388 AF XY: 0.00

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

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 Cov.: 31

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152264 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74394

African (AFR) AF: 0.000145 AC: 6 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68048

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.3
DANN	Benign	0.92
DEOGEN2	Benign	0.078	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.27
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.042
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.045	D
Polyphen		0.0070	B
Vest4		0.19
MVP		0.055
MPC		0.17
ClinPred		0.20	T
GERP RS		0.76
Varity_R		0.15
gMVP		0.044
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs146859197; hg19: chr11-133711956;