chr1-217782257-T-G

Variant names:

• chr1-217782257-T-G
• NM_138796.4:c.807T>G
• SPATA17 p.Asp269Glu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138796.4(SPATA17):​c.807T>G​(p.Asp269Glu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D269N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SPATA17 NM_138796.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08902714).

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.807T>G	p.Asp269Glu	missense	Exon 8 of 11	NP_620151.1	Q96L03
	SPATA17	NM_001375655.1		c.807T>G	p.Asp269Glu	missense	Exon 8 of 11	NP_001362584.1	Q96L03
	SPATA17-AS1	NR_125784.1		n.202A>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA17	ENST00000366933.5	TSL:1 MANE Select	c.807T>G	p.Asp269Glu	missense	Exon 8 of 11	ENSP00000355900.4	Q96L03
	SPATA17	ENST00000905764.1		c.807T>G	p.Asp269Glu	missense	Exon 8 of 12	ENSP00000575823.1
	SPATA17	ENST00000937952.1		c.756T>G	p.Asp252Glu	missense	Exon 7 of 10	ENSP00000608011.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000487 AC: 71 AN: 1458028 Hom.: 0 Cov.: 30 AF XY: 0.0000386 AC XY: 28 AN XY: 725364

⚠️ 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: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26072

East Asian (EAS) AF: 0.00 AC: 0 AN: 39632

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.0000559 AC: 62 AN: 1108920

Other (OTH) AF: 0.0000996 AC: 6 AN: 60232

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.099
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.018
Sift	Benign	0.18	T
Sift4G	Benign	0.13	T
Varity_R		0.041
gMVP		0.16
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-217955599;