Genetic Variant NM_174927.3:c.271A>G (chr11-133844334-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_174927.3(SPATA19):c.271A>G(p.Lys91Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SPATA19
NM_174927.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA19	NM_174927.3 link	c.271A>G	p.Lys91Glu	missense_variant	Exon 4 of 7	ENST00000299140.8	NP_777587.1	Q7Z5L4A0A140VKB6
SPATA19	NM_001291992.2 link	c.271A>G	p.Lys91Glu	missense_variant	Exon 4 of 7		NP_001278921.1	Q7Z5L4A0A140VKB6
SPATA19	XR_947806.2 link	n.338A>G		non_coding_transcript_exon_variant	Exon 4 of 8
SPATA19	XR_947807.2 link	n.338A>G		non_coding_transcript_exon_variant	Exon 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA19	ENST00000299140.8 link	c.271A>G	p.Lys91Glu	missense_variant	Exon 4 of 7	1	NM_174927.3	ENSP00000299140.3		Q7Z5L4
SPATA19	ENST00000532889.1 link	c.271A>G	p.Lys91Glu	missense_variant	Exon 4 of 7	5		ENSP00000435248.1		Q7Z5L4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.271A>G (p.K91E) alteration is located in exon 4 (coding exon 4) of the SPATA19 gene. This alteration results from a A to G substitution at nucleotide position 271, causing the lysine (K) at amino acid position 91 to be replaced by a glutamic acid (E). 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

0.33

BayesDel_addAF

Uncertain

0.094

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.5

L;L

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.19

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.99

D;D

Vest4

0.60

MutPred

0.33

Loss of methylation at K91 (P = 0.0173);Loss of methylation at K91 (P = 0.0173);

MVP

0.18

MPC

0.071

ClinPred

0.97

GERP RS

5.5

Varity_R

0.62

gMVP

0.020

Splicing

Name

Calibrated prediction

Score

Prediction

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

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