1-1427696-G-T

Variant names:

• chr1-1427696-G-T
• rs1317865800
• NM_001146685.2:c.401G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146685.2(TMEM278):​c.401G>T​(p.Arg134Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,181,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R134H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: TMEM278 NM_001146685.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0310
• Publications: 0 publications found

Genes affected

TMEM278 (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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21980938).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146685.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM278	NM_001146685.2	MANE Select	c.401G>T	p.Arg134Leu	missense	Exon 2 of 2	NP_001140157.1	A6NKF7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM88B	ENST00000378821.4	TSL:2 MANE Select	c.401G>T	p.Arg134Leu	missense	Exon 2 of 2	ENSP00000455099.1	A6NKF7

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD2 exomes AF: 0.0000223 AC: 1 AN: 44748 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000155

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000169 AC: 2 AN: 1181970 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 578072

African (AFR) AF: 0.00 AC: 0 AN: 23804

American (AMR) AF: 0.0000633 AC: 1 AN: 15796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18034

East Asian (EAS) AF: 0.00 AC: 0 AN: 25652

South Asian (SAS) AF: 0.0000208 AC: 1 AN: 47974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3374

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 973452

Other (OTH) AF: 0.00 AC: 0 AN: 47044

GnomAD4 genome Cov.: 18

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.54	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.22	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.031
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.3	N
Sift	Uncertain	0.013	D
Sift4G	Benign	0.089	T
Polyphen		0.76	P
Vest4		0.22
MVP		0.76
GERP RS		1.7
Varity_R		0.20
gMVP		0.10
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1317865800; hg19: chr1-1363076;