1-48359765-G-C

Position:

• chr1-48359765-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_019073.4(SPATA6):​c.915C>G​(p.Ile305Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA6 NM_019073.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.345

Genes affected

SPATA6 (HGNC:18309): (spermatogenesis associated 6) Predicted to enable myosin light chain binding activity. Predicted to be involved in motile cilium assembly and spermatogenesis. Predicted to be located in extracellular region. Predicted to be active in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11234909).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA6	NM_019073.4	c.915C>G	p.Ile305Met	missense_variant	10/13	ENST00000371847.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA6	ENST00000371847.8	c.915C>G	p.Ile305Met	missense_variant	10/13	1	NM_019073.4	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.915C>G (p.I305M) alteration is located in exon 10 (coding exon 10) of the SPATA6 gene. This alteration results from a C to G substitution at nucleotide position 915, causing the isoleucine (I) at amino acid position 305 to be replaced by a methionine (M). 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	0.077
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.031	T;T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.60	N;.;N;N
REVEL	Benign	0.032
Sift	Benign	0.13	T;.;T;T
Sift4G	Benign	0.24	T;T;T;.
Polyphen		0.0070	B;.;B;.
Vest4		0.16
MutPred		0.27		Gain of ubiquitination at K300 (P = 0.0441);.;Gain of ubiquitination at K300 (P = 0.0441);.;
MVP		0.099
MPC		0.053
ClinPred		0.078	T
GERP RS		3.0
Varity_R		0.068
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-48825437; COSMIC: COSV100893373; COSMIC: COSV100893373;