16-57977995-G-C

Position:

• chr16-57977995-G-C

Variant summary

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

The ENST00000441824.4(TEPP):​c.179G>C​(p.Cys60Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEPP ENST00000441824.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPMIP8	NM_199456.3	c.179G>C	p.Cys60Ser	missense_variant	2/8	ENST00000441824.4	NP_955535.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEPP	ENST00000441824.4	c.179G>C	p.Cys60Ser	missense_variant	2/8	1	NM_199456.3	ENSP00000401917.3
TEPP	ENST00000290871.10	c.179G>C	p.Cys60Ser	missense_variant	2/8	1		ENSP00000290871.6
TEPP	ENST00000569996.5	n.57+1361G>C		intron_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000935 Hom.: 0

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

Feb 09, 2022

The c.344G>C (p.C115S) alteration is located in exon 2 (coding exon 2) of the TEPP gene. This alteration results from a G to C substitution at nucleotide position 344, causing the cysteine (C) at amino acid position 115 to be replaced by a serine (S). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.079	.;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	0.55	D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.19
Sift	Benign	0.12	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.97	D;P
Vest4		0.52
MutPred		0.47		Gain of disorder (P = 0.0082);Gain of disorder (P = 0.0082);
MVP		0.57
MPC		0.77
ClinPred		0.76	D
GERP RS		3.4
Varity_R		0.10
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs1962703671; hg19: chr16-58011899;