1-1426136-G-T

Variant names:

• chr1-1426136-G-T
• NM_001146685.2:c.9G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001146685.2(TMEM88B):​c.9G>T​(p.Glu3Asp) 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. 12/18 in silico tools predict 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: TMEM88B NM_001146685.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.77

Genes affected

TMEM88B (HGNC:37099): (transmembrane protein 88B) Predicted to enable PDZ domain binding activity. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.029613137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM88B	NM_001146685.2	c.9G>T	p.Glu3Asp	missense_variant	Exon 1 of 2	ENST00000378821.4	NP_001140157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM88B	ENST00000378821.4	c.9G>T	p.Glu3Asp	missense_variant	Exon 1 of 2	2	NM_001146685.2	ENSP00000455099.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1252934 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 608376

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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 02, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.9G>T (p.E3D) alteration is located in exon 1 (coding exon 1) of the TMEM88B gene. This alteration results from a G to T substitution at nucleotide position 9, causing the glutamic acid (E) at amino acid position 3 to be replaced by an aspartic acid (D). 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	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.74
DANN	Benign	0.89
DEOGEN2	Benign	0.0023	T
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.030	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.64	N
Sift	Benign	1.0	T
Sift4G	Benign	0.35	T
Polyphen		0.0020	B
Vest4		0.12
MVP		0.48
GERP RS		-2.7
Varity_R		0.038
gMVP		0.079

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: chr1-1361516;