14-56585809-G-A

Position:

• chr14-56585809-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017799.4(TMEM260):​c.241G>A​(p.Ala81Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000021 (0 hom.)
• Consequence: TMEM260 NM_017799.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.29

Genes affected

TMEM260 (HGNC:20185): (transmembrane protein 260) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1891703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM260	NM_017799.4	c.241G>A	p.Ala81Thr	missense_variant	3/16	ENST00000261556.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM260	ENST00000261556.11	c.241G>A	p.Ala81Thr	missense_variant	3/16	2	NM_017799.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461108 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726840

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: 0.00000270

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

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.241G>A (p.A81T) alteration is located in exon 3 (coding exon 3) of the TMEM260 gene. This alteration results from a G to A substitution at nucleotide position 241, causing the alanine (A) at amino acid position 81 to be replaced by a threonine (T). 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	0.086
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.017	.;T;.
Eigen	Benign	-0.13
Eigen_PC	Benign	0.049
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;L
MutationTaster	Benign	0.79	D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.056
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.032	.;B;.
Vest4		0.47, 0.46
MutPred		0.38		.;Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.30
MPC		0.031
ClinPred		0.59	D
GERP RS		4.7
Varity_R		0.046
gMVP		0.63

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: chr14-57052527;