chr17-45255392-T-A

Variant names:

• chr17-45255392-T-A
• NM_152343.3:c.790A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152343.3(SPATA32):​c.790A>T​(p.Met264Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M264T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPATA32 NM_152343.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.309
• Publications: 0 publications found

Genes affected

SPATA32 (HGNC:26349): (spermatogenesis associated 32) Predicted to enable actin binding activity. Predicted to be involved in spermatogenesis. Predicted to be active in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MAP3K14-AS1 (HGNC:44359): (MAP3K14 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.043853402).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152343.3. 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
	SPATA32	NM_152343.3	MANE Select	c.790A>T	p.Met264Leu	missense	Exon 4 of 5	NP_689556.2	Q96LK8
	MAP3K14-AS1	NR_024434.2		n.79+7389T>A		intron	N/A
	MAP3K14-AS1	NR_110325.1		n.259+174T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA32	ENST00000331780.5	TSL:1 MANE Select	c.790A>T	p.Met264Leu	missense	Exon 4 of 5	ENSP00000331532.4	Q96LK8
	MAP3K14-AS1	ENST00000590100.7	TSL:1	n.70+7389T>A		intron	N/A
	SPATA32	ENST00000586359.1	TSL:2	n.*1308A>T		non_coding_transcript_exon	Exon 6 of 7	ENSP00000467344.1	K7EPE1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.21
DANN	Benign	0.76
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.31
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.011
Sift	Benign	0.26	T
Sift4G	Benign	0.19	T
Polyphen		0.0020	B
Vest4		0.092
MutPred		0.19		Loss of helix (P = 0.1706)
MVP		0.030
MPC		0.17
ClinPred		0.056	T
GERP RS		1.0
Varity_R		0.096
gMVP		0.057

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

hg19: chr17-43332759;