chr17-7432736-T-G

Variant names:

• chr17-7432736-T-G
• rs4796305
• NM_001364708.1:c.3565T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

Genes affected

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

ENSG00000286007 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364708.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEM3	NM_001364708.1	MANE Select	c.3565T>G	p.Ser1189Ala	missense	Exon 3 of 3	NP_001351637.1
	SPEM3	NM_001364672.1		c.3466T>G	p.Ser1156Ala	missense	Exon 3 of 3	NP_001351601.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEM3	ENST00000636696.4	TSL:5 MANE Select	c.3565T>G	p.Ser1189Ala	missense	Exon 3 of 3	ENSP00000490274.1
	ENSG00000286007	ENST00000651314.1		n.197-3117T>G		intron	N/A	ENSP00000498964.1
	ENSG00000262880	ENST00000575310.1	TSL:2	n.273-8735T>G		intron	N/A

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

African (AFR) AF: 0.0469 AC: 337 AN: 7182

American (AMR) AF: 0.0492 AC: 366 AN: 7434

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 573 AN: 9240

East Asian (EAS) AF: 0.0228 AC: 521 AN: 22894

South Asian (SAS) AF: 0.180 AC: 543 AN: 3024

European-Finnish (FIN) AF: 0.0934 AC: 1946 AN: 20832

Middle Eastern (MID) AF: 0.0572 AC: 74 AN: 1294

European-Non Finnish (NFE) AF: 0.0843 AC: 13321 AN: 158070

Other (OTH) AF: 0.0787 AC: 1289 AN: 16376

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

African (AFR) AF: 0.0472 AC: 1961 AN: 41548

American (AMR) AF: 0.0511 AC: 782 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 184 AN: 3470

East Asian (EAS) AF: 0.0371 AC: 192 AN: 5182

South Asian (SAS) AF: 0.160 AC: 770 AN: 4820

European-Finnish (FIN) AF: 0.0853 AC: 904 AN: 10592

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5829 AN: 68016

Other (OTH) AF: 0.0648 AC: 137 AN: 2114

Alfa AF: 0.0861 Hom.: 532

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 v4.9

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
PhyloP100		-2.4
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

Other links and lift over

dbSNP: rs4796305; hg19: chr17-7336055;