chr17-7427126-C-A

Variant names:

• chr17-7427126-C-A
• NM_175734.5:c.1135C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175734.5(SPEM2):​c.1135C>A​(p.Arg379Ser) 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. 13/19 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R379C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPEM2 NM_175734.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07922134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPEM2	NM_175734.5	c.1135C>A	p.Arg379Ser	missense_variant	Exon 3 of 3	ENST00000333870.8	NP_783861.3
SPEM2	XM_006721471.4	c.844C>A	p.Arg282Ser	missense_variant	Exon 3 of 3		XP_006721534.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPEM2	ENST00000333870.8	c.1135C>A	p.Arg379Ser	missense_variant	Exon 3 of 3	1	NM_175734.5	ENSP00000328061.3
SPEM2	ENST00000574034.1	c.*419C>A		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000458799.1
ENSG00000262880	ENST00000575310.1	n.272+5525C>A		intron_variant	Intron 3 of 5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.22
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.022	D
Polyphen		0.0	B
Vest4		0.22
MutPred		0.25		Loss of MoRF binding (P = 0.0209);
MVP		0.27
MPC		0.20
ClinPred		0.23	T
GERP RS		3.8
Varity_R		0.10
gMVP		0.031

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-7330445;