rs114098188

Variant names:

• chr1-217782313-A-T
• rs114098188
• NM_138796.4:c.863A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-217782313-A-T
• chr1-217782313-A-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_138796.4(SPATA17):​c.863A>T​(p.Asn288Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000551 in 1,608,006 control chromosomes in the GnomAD database, including 3 homozygotes. 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N288K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (2 hom.)
• Consequence: SPATA17 NM_138796.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 2.00
• 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]

SPATA17-AS1 (HGNC:41086): (SPATA17 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009138256).
• BP6: Variant 1-217782313-A-T is Benign according to our data. Variant chr1-217782313-A-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 2639902.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.863A>T	p.Asn288Ile	missense	Exon 8 of 11	NP_620151.1	Q96L03
	SPATA17	NM_001375655.1		c.863A>T	p.Asn288Ile	missense	Exon 8 of 11	NP_001362584.1	Q96L03
	SPATA17-AS1	NR_125784.1		n.160-14T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA17	ENST00000366933.5	TSL:1 MANE Select	c.863A>T	p.Asn288Ile	missense	Exon 8 of 11	ENSP00000355900.4	Q96L03
	SPATA17	ENST00000905764.1		c.863A>T	p.Asn288Ile	missense	Exon 8 of 12	ENSP00000575823.1
	SPATA17	ENST00000937952.1		c.812A>T	p.Asn271Ile	missense	Exon 7 of 10	ENSP00000608011.1

Frequencies

GnomAD3 genomes AF: 0.00271 AC: 413 AN: 152196 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00859

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00308

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.000720 AC: 177 AN: 245686 AF XY: 0.000527

Gnomad AFR exome AF: 0.00869

Gnomad AMR exome AF: 0.000609

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000107

Gnomad OTH exome AF: 0.000834

GnomAD4 exome AF: 0.000323 AC: 470 AN: 1455692 Hom.: 2 Cov.: 30 AF XY: 0.000293 AC XY: 212 AN XY: 724220

African (AFR) AF: 0.00970 AC: 321 AN: 33088

American (AMR) AF: 0.000949 AC: 41 AN: 43208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25804

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.00140 AC: 8 AN: 5726

European-Non Finnish (NFE) AF: 0.0000451 AC: 50 AN: 1109686

Other (OTH) AF: 0.000815 AC: 49 AN: 60130

GnomAD4 genome AF: 0.00273 AC: 416 AN: 152314 Hom.: 1 Cov.: 32 AF XY: 0.00258 AC XY: 192 AN XY: 74490

African (AFR) AF: 0.00863 AC: 359 AN: 41576

American (AMR) AF: 0.00307 AC: 47 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00237 AC: 5 AN: 2108

Alfa AF: 0.000424 Hom.: 0

Bravo AF: 0.00337

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00862 AC: 38

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000931 AC: 113

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.8
DANN	Benign	0.59
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0091	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		2.0
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.044
Sift	Benign	0.42	T
Sift4G	Benign	0.39	T
Polyphen		0.068	B
Vest4		0.27
MVP		0.14
MPC		0.030
ClinPred		0.011	T
GERP RS		2.4
Varity_R		0.20
gMVP		0.43
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs114098188; hg19: chr1-217955655;