11-133845189-T-A

Variant names:

• chr11-133845189-T-A
• NM_174927.3:c.80A>T

Variant summary

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

The NM_174927.3(SPATA19):​c.80A>T​(p.Asp27Val) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA19 NM_174927.3 missense, splice_region
• Scores: Splicing: ADA: 0.5861
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.80A>T	p.Asp27Val	missense splice_region	Exon 2 of 7	NP_777587.1	A0A140VKB6
	SPATA19	NM_001291992.2		c.80A>T	p.Asp27Val	missense splice_region	Exon 2 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.80A>T	p.Asp27Val	missense splice_region	Exon 2 of 7	ENSP00000299140.3	Q7Z5L4
	SPATA19	ENST00000532889.1	TSL:5	c.80A>T	p.Asp27Val	missense splice_region	Exon 2 of 7	ENSP00000435248.1	Q7Z5L4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.6	L
PhyloP100		3.6
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-8.6	D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.57
MutPred		0.45		Gain of sheet (P = 0.0101)
MVP		0.50
MPC		0.39
ClinPred		1.0	D
GERP RS		5.3
PromoterAI		-0.021	Neutral
Varity_R		0.87
gMVP		0.62
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.59
dbscSNV1_RF	Benign	0.64
SpliceAI score (max)		0.0		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

hg19: chr11-133715084;