17-7855698-G-T

Position:

• chr17-7855698-G-T

Variant summary

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

The NM_203411.2(TMEM88):​c.464G>T​(p.Gly155Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM88 NM_203411.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36

Genes affected

TMEM88 (HGNC:32371): (transmembrane protein 88) Predicted to enable PDZ domain binding activity. Involved in negative regulation of canonical Wnt signaling pathway; protein localization to plasma membrane; and protein stabilization. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.2531436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM88	NM_203411.2	c.464G>T	p.Gly155Val	missense_variant	2/2	ENST00000301599.7	NP_981956.1
TMEM88	XM_005256856.4	c.506G>T	p.Gly169Val	missense_variant	2/2		XP_005256913.1
TMEM88	NM_001319941.1	c.211-73G>T		intron_variant			NP_001306870.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM88	ENST00000301599.7	c.464G>T	p.Gly155Val	missense_variant	2/2	1	NM_203411.2	ENSP00000301599.6
TMEM88	ENST00000574668.1	c.211-73G>T		intron_variant		2		ENSP00000459725.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1430268 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 708460

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000839 AC: 1

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

Oct 19, 2021

The c.464G>T (p.G155V) alteration is located in exon 2 (coding exon 2) of the TMEM88 gene. This alteration results from a G to T substitution at nucleotide position 464, causing the glycine (G) at amino acid position 155 to be replaced by a valine (V). 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	0.21
BayesDel_addAF	Benign	-0.092	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.049
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.21
Sift	Benign	0.24	T
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.17
MutPred		0.29		Gain of sheet (P = 0.0073);
MVP		0.061
MPC		2.3
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.43
gMVP		0.69

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: rs747316854; hg19: chr17-7759016;