chr14-56532814-A-G

Variant names:

• chr14-56532814-A-G
• rs1959068
• ENST00000557246.1:n.188-16457A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000556810.5(TMEM260):​c.49+41233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,134 control chromosomes in the GnomAD database, including 11,724 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (11724 hom., cov: 33)
• Consequence: TMEM260 ENST00000556810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.64
• Publications: 4 publications found

Genes affected

ENSG00000258803 (HGNC:):

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

TMEM260 Gene-Disease associations (from GenCC):

• structural heart defects and renal anomalies syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000556810.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOC101927690	NR_135241.1		n.188-16457A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000258803	ENST00000557246.1	TSL:1	n.188-16457A>G		intron	N/A
	TMEM260	ENST00000556810.5	TSL:3	c.49+41233A>G		intron	N/A	ENSP00000451677.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57444 AN: 152018 Hom.: 11721 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.389

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.378 AC: 57460 AN: 152134 Hom.: 11724 Cov.: 33 AF XY: 0.381 AC XY: 28331 AN XY: 74362

African (AFR) AF: 0.273 AC: 11346 AN: 41508

American (AMR) AF: 0.506 AC: 7730 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1255 AN: 3472

East Asian (EAS) AF: 0.747 AC: 3862 AN: 5172

South Asian (SAS) AF: 0.556 AC: 2681 AN: 4820

European-Finnish (FIN) AF: 0.329 AC: 3476 AN: 10576

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25827 AN: 67978

Other (OTH) AF: 0.390 AC: 825 AN: 2116

Alfa AF: 0.379 Hom.: 35369

Bravo AF: 0.387

Asia WGS AF: 0.585 AC: 2029 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.77
PhyloP100		2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1959068; hg19: chr14-56999532;