rs1049461881

Variant names:

• chr1-217648969-C-G
• rs1049461881
• NM_138796.4:c.156C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-217648969-C-G
• chr1-217648969-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138796.4(SPATA17):​c.156C>G​(p.Ile52Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: SPATA17 NM_138796.4 missense, splice_region
• Scores: Splicing: ADA: 0.001295
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.459
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2854017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138796.4. 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
	SPATA17	NM_138796.4	MANE Select	c.156C>G	p.Ile52Met	missense splice_region	Exon 2 of 11	NP_620151.1	Q96L03
	SPATA17	NM_001375655.1		c.156C>G	p.Ile52Met	missense splice_region	Exon 2 of 11	NP_001362584.1	Q96L03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA17	ENST00000366933.5	TSL:1 MANE Select	c.156C>G	p.Ile52Met	missense splice_region	Exon 2 of 11	ENSP00000355900.4	Q96L03
	SPATA17	ENST00000905764.1		c.156C>G	p.Ile52Met	missense splice_region	Exon 2 of 12	ENSP00000575823.1
	SPATA17	ENST00000937952.1		c.156C>G	p.Ile52Met	missense splice_region	Exon 2 of 10	ENSP00000608011.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000812 AC: 2 AN: 246446 AF XY: 0.00000751

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000304

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1452054 Hom.: 0 Cov.: 28 AF XY: 0.00000692 AC XY: 5 AN XY: 722456

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33174

American (AMR) AF: 0.0000232 AC: 1 AN: 43084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25930

East Asian (EAS) AF: 0.00 AC: 0 AN: 39394

South Asian (SAS) AF: 0.00 AC: 0 AN: 84494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.00000452 AC: 5 AN: 1107056

Other (OTH) AF: 0.00 AC: 0 AN: 59948

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000304987), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	0.096
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.088
Eigen_PC	Benign	0.082
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.46
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Benign	0.069	T
Polyphen		0.92	P
Vest4		0.35
MutPred		0.53		Gain of methylation at R53 (P = 0.0468)
MVP		0.45
MPC		0.076
ClinPred		0.42	T
GERP RS		2.3
Varity_R		0.078
gMVP		0.48
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0013
dbscSNV1_RF	Benign	0.042
SpliceAI score (max)		0.010		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: rs1049461881; hg19: chr1-217822311;