chr1-1427696-G-A

Variant names:

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

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>A​(p.Arg134His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 1,181,968 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R134L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0000068 (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=0.096227676).

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>A	p.Arg134His	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>A	p.Arg134His	missense	Exon 2 of 2	ENSP00000455099.1	A6NKF7

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome AF: 0.00000677 AC: 8 AN: 1181968 Hom.: 0 Cov.: 34 AF XY: 0.00000173 AC XY: 1 AN XY: 578070

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

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 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: 0.00000719 AC: 7 AN: 973450

Other (OTH) AF: 0.0000213 AC: 1 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	0.12
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.096	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.031
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.9	N
Sift	Benign	0.13	T
Sift4G	Benign	0.20	T
Polyphen		0.049	B
Vest4		0.15
MVP		0.54
GERP RS		1.7
Varity_R		0.082
gMVP		0.061
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;