NM_175734.5:c.1151G>A

Variant names:

• chr17-7427142-G-A
• rs572068639
• NM_175734.5:c.1151G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_175734.5(SPEM2):​c.1151G>A​(p.Arg384Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,613,350 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000076 (1 hom.)
• Consequence: SPEM2 NM_175734.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.936
• Publications: 1 publications found

Genes affected

SPEM2 (HGNC:27315): (SPEM family member 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000262880 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.07467872).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175734.5. 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
	SPEM2	NM_175734.5	MANE Select	c.1151G>A	p.Arg384Gln	missense	Exon 3 of 3	NP_783861.3	Q0P670

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPEM2	ENST00000333870.8	TSL:1 MANE Select	c.1151G>A	p.Arg384Gln	missense	Exon 3 of 3	ENSP00000328061.3	Q0P670
	SPEM2	ENST00000574034.1	TSL:1	c.*435G>A		3_prime_UTR	Exon 3 of 3	ENSP00000458799.1	I3L1F6
	ENSG00000262880	ENST00000575310.1	TSL:2	n.272+5541G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000850 AC: 21 AN: 247110 AF XY: 0.0000968

Gnomad AFR exome AF: 0.000326

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000167

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000179

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000760 AC: 111 AN: 1461038 Hom.: 1 Cov.: 34 AF XY: 0.0000784 AC XY: 57 AN XY: 726788

African (AFR) AF: 0.000388 AC: 13 AN: 33470

American (AMR) AF: 0.0000672 AC: 3 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39692

South Asian (SAS) AF: 0.000279 AC: 24 AN: 86140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000594 AC: 66 AN: 1111670

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152312 Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8 AN XY: 74470

African (AFR) AF: 0.000457 AC: 19 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000996 Hom.: 0

Bravo AF: 0.000117

ExAC AF: 0.0000991 AC: 12

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

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	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	15
DANN	Benign	0.90
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.071	N
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.94
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.084
Sift	Benign	0.034	D
Sift4G	Uncertain	0.059	T
Polyphen		0.97	D
Vest4		0.21
MVP		0.25
MPC		0.22
ClinPred		0.055	T
GERP RS		2.8
Varity_R		0.079
gMVP		0.047
Mutation Taster		=93/7	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: rs572068639; hg19: chr17-7330461; COSMIC: COSV61603323; COSMIC: COSV61603323;