1-1427587-C-G

Variant names:

• chr1-1427587-C-G
• rs1282933314
• NM_001146685.2:c.292C>G

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.292C>G​(p.Leu98Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000872 in 1,147,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 12)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TMEM278 NM_001146685.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.221
• 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=0.09838402).

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.292C>G	p.Leu98Val	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.292C>G	p.Leu98Val	missense	Exon 2 of 2	ENSP00000455099.1	A6NKF7

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 89312 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 41850 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 8.72e-7 AC: 1 AN: 1147320 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 556302

African (AFR) AF: 0.00 AC: 0 AN: 23694

American (AMR) AF: 0.00 AC: 0 AN: 13546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17294

East Asian (EAS) AF: 0.00 AC: 0 AN: 26178

South Asian (SAS) AF: 0.00 AC: 0 AN: 38806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3280

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 954256

Other (OTH) AF: 0.00 AC: 0 AN: 45634

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 89312 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 42966

African (AFR) AF: 0.00 AC: 0 AN: 21422

American (AMR) AF: 0.00 AC: 0 AN: 9066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2294

East Asian (EAS) AF: 0.00 AC: 0 AN: 3034

South Asian (SAS) AF: 0.00 AC: 0 AN: 2454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 186

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 43560

Other (OTH) AF: 0.00 AC: 0 AN: 1112

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	0.079
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	10
DANN	Benign	0.77
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.098	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.22
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.9	N
Sift	Benign	0.14	T
Sift4G	Benign	0.29	T
Polyphen		0.040	B
Vest4		0.15
MVP		0.45
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.095
gMVP		0.066
Mutation Taster		=97/3	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: rs1282933314; hg19: chr1-1362967;