rs4796305

chr17-7432736-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364708.1(SPEM3):c.3565T>G(p.Ser1189Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0747 in 398,586 control chromosomes in the GnomAD database, including 1,314 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.071 (458 hom., cov: 32)
  • Exomes 𝑓: 0.077 (856 hom.)
• Consequence: SPEM3 NM_001364708.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.38

Genes affected

SPEM3 (HGNC:53651): (SPEM family member 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019609928).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPEM3	NM_001364708.1	c.3565T>G	p.Ser1189Ala	missense_variant	3/3	ENST00000636696.4
SPEM3	NM_001364672.1	c.3466T>G	p.Ser1156Ala	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPEM3	ENST00000636696.4	c.3565T>G	p.Ser1189Ala	missense_variant	3/3	5	NM_001364708.1	P1

Frequencies

GnomAD3 genomes AF: 0.0709 AC: 10786 AN: 152122 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0375

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0853

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0636

GnomAD4 exome AF: 0.0770 AC: 18970 AN: 246346 Hom.: 856 Cov.: 0 AF XY: 0.0774 AC XY: 9664 AN XY: 124826

Gnomad4 AFR exome AF: 0.0469

Gnomad4 AMR exome AF: 0.0492

Gnomad4 ASJ exome AF: 0.0620

Gnomad4 EAS exome AF: 0.0228

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.0934

Gnomad4 NFE exome AF: 0.0843

Gnomad4 OTH exome AF: 0.0787

GnomAD4 genome AF: 0.0709 AC: 10787 AN: 152240 Hom.: 458 Cov.: 32 AF XY: 0.0713 AC XY: 5309 AN XY: 74422

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.0371

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0853

Gnomad4 NFE AF: 0.0857

Gnomad4 OTH AF: 0.0648

Alfa AF: 0.0881 Hom.: 352

Bravo AF: 0.0644

TwinsUK AF: 0.0809 AC: 300

ALSPAC AF: 0.0812 AC: 313

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.040
Dann	Benign	0.67
DEOGEN2	Benign	0.0067	T
FATHMM_MKL	Benign	0.0066	N
MetaRNN	Benign	0.0020	T
GERP RS		-6.0
Varity_R		0.049
gMVP		0.00058

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4796305; hg19: chr17-7336055;