1-1426174-G-C

Position:

• chr1-1426174-G-C

Variant summary

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

The NM_001146685.2(TMEM88B):​c.47G>C​(p.Gly16Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000079 in 1,266,156 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 7.9e-7 (0 hom.)
• Consequence: TMEM88B NM_001146685.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.155

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=0.06324488).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM88B	NM_001146685.2	c.47G>C	p.Gly16Ala	missense_variant	1/2	ENST00000378821.4	NP_001140157.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM88B	ENST00000378821.4	c.47G>C	p.Gly16Ala	missense_variant	1/2	2	NM_001146685.2	ENSP00000455099	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.90e-7 AC: 1 AN: 1266156 Hom.: 0 Cov.: 32 AF XY: 0.00000162 AC XY: 1 AN XY: 616192

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: 9.86e-7

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 15, 2024

The c.47G>C (p.G16A) alteration is located in exon 1 (coding exon 1) of the TMEM88B gene. This alteration results from a G to C substitution at nucleotide position 47, causing the glycine (G) at amino acid position 16 to be replaced by an alanine (A). 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	0.085
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.1
DANN	Benign	0.34
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.063	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.25	N
Sift	Benign	1.0	T
Sift4G	Benign	0.17	T
Polyphen		0.21	B
Vest4		0.16
MVP		0.43
GERP RS		0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.032
gMVP		0.085

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: chr1-1361554;