1-1427608-G-A

Variant names:

• chr1-1427608-G-A
• rs1264284614
• NM_001146685.2:c.313G>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.313G>A​(p.Ala105Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000368 in 1,087,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A105P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 14)
  • Exomes 𝑓: 0.0000037 (0 hom.)
• Consequence: TMEM278 NM_001146685.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• 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=0.13313389).

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.313G>A	p.Ala105Thr	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.313G>A	p.Ala105Thr	missense	Exon 2 of 2	ENSP00000455099.1	A6NKF7

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD2 exomes AF: 0.00 AC: 0 AN: 61892 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: 0.00000368 AC: 4 AN: 1087008 Hom.: 0 Cov.: 34 AF XY: 0.00000189 AC XY: 1 AN XY: 528174

African (AFR) AF: 0.00 AC: 0 AN: 21650

American (AMR) AF: 0.00 AC: 0 AN: 15906

Ashkenazi Jewish (ASJ) AF: 0.0000641 AC: 1 AN: 15606

East Asian (EAS) AF: 0.0000549 AC: 1 AN: 18220

South Asian (SAS) AF: 0.00 AC: 0 AN: 46888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2880

European-Non Finnish (NFE) AF: 0.00000220 AC: 2 AN: 907034

Other (OTH) AF: 0.00 AC: 0 AN: 40482

GnomAD4 genome Cov.: 14

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0059	T
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.13	T
MutationAssessor	Benign	1.3	L
PhyloP100		1.5
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.3	N
Sift	Benign	0.068	T
Sift4G	Benign	0.60	T
Polyphen		0.22	B
Vest4		0.39
MVP		0.47
GERP RS		0.45
Varity_R		0.094
gMVP		0.052
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1264284614; hg19: chr1-1362988;