1-217774520-A-G

Variant names:

• chr1-217774520-A-G
• NM_138796.4:c.706A>G

Variant summary

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

The NM_138796.4(SPATA17):​c.706A>G​(p.Asn236Asp) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATA17 NM_138796.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.892

Genes affected

SPATA17 (HGNC:25184): (spermatogenesis associated 17) Predicted to enable calmodulin binding activity. Predicted to be located in cytoplasm. [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=0.014287859).
• BP6: Variant 1-217774520-A-G is Benign according to our data. Variant chr1-217774520-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2624234.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA17	NM_138796.4	c.706A>G	p.Asn236Asp	missense_variant	Exon 7 of 11	ENST00000366933.5	NP_620151.1
SPATA17	NM_001375655.1	c.706A>G	p.Asn236Asp	missense_variant	Exon 7 of 11		NP_001362584.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA17	ENST00000366933.5	c.706A>G	p.Asn236Asp	missense_variant	Exon 7 of 11	1	NM_138796.4	ENSP00000355900.4
SPATA17	ENST00000492747.2	n.552A>G		non_coding_transcript_exon_variant	Exon 4 of 6	5
SPATA17	ENST00000470448.5	n.*645A>G		downstream_gene_variant		3		ENSP00000473514.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 14, 2023

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	0.067
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.28
DANN	Benign	0.60
DEOGEN2	Benign	0.0053	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.26	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.047
Sift	Benign	0.99	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.19		Gain of ubiquitination at K238 (P = 0.0505);
MVP		0.030
MPC		0.025
ClinPred		0.025	T
GERP RS		-6.3
Varity_R		0.045
gMVP		0.12

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: chr1-217947862;