16-57985209-A-G

Position:

• chr16-57985209-A-G

Variant summary

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

The ENST00000441824.4(TEPP):​c.464A>G​(p.Glu155Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000362 in 1,380,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: TEPP ENST00000441824.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.668

Genes affected

SPMIP8 (HGNC:33745): (sperm microtubule inner protein 8) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

TEPP (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=0.119993776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPMIP8	NM_199456.3	c.464A>G	p.Glu155Gly	missense_variant	5/8	ENST00000441824.4	NP_955535.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEPP	ENST00000441824.4	c.464A>G	p.Glu155Gly	missense_variant	5/8	1	NM_199456.3	ENSP00000401917.3
TEPP	ENST00000290871.10	c.464A>G	p.Glu155Gly	missense_variant	5/8	1		ENSP00000290871.6
TEPP	ENST00000562915.1	n.29A>G		non_coding_transcript_exon_variant	1/3	2
TEPP	ENST00000569996.5	n.298A>G		non_coding_transcript_exon_variant	4/8	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000362 AC: 5 AN: 1380380 Hom.: 0 Cov.: 41 AF XY: 0.00000441 AC XY: 3 AN XY: 679586

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000466

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.629A>G (p.E210G) alteration is located in exon 5 (coding exon 5) of the TEPP gene. This alteration results from a A to G substitution at nucleotide position 629, causing the glutamic acid (E) at amino acid position 210 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.17	.;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.35	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.072
Sift	Benign	0.37	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0040	B;B
Vest4		0.41
MutPred		0.29		Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);
MVP		0.31
MPC		0.27
ClinPred		0.41	T
GERP RS		2.9
Varity_R		0.11
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs889975591; hg19: chr16-58019113;