chr14-56586179-G-A

Variant names:

• chr14-56586179-G-A
• rs7141305
• NM_017799.4:c.344+267G>A

Variant summary

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

The NM_017799.4(TMEM260):​c.344+267G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,132 control chromosomes in the GnomAD database, including 60,490 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 0.89 (60490 hom., cov: 32)
• Consequence: TMEM260 NM_017799.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.125
• Publications: 1 publications found

Genes affected

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017799.4. 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
	TMEM260	NM_017799.4	MANE Select	c.344+267G>A		intron	N/A	NP_060269.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM260	ENST00000261556.11	TSL:2 MANE Select	c.344+267G>A		intron	N/A	ENSP00000261556.6
	TMEM260	ENST00000538838.5	TSL:1	c.344+267G>A		intron	N/A	ENSP00000441934.1
	TMEM260	ENST00000539559.6	TSL:1	n.344+267G>A		intron	N/A	ENSP00000442602.2

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135338 AN: 152014 Hom.: 60427 Cov.: 32

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.874

Gnomad OTH AF: 0.877

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

GnomAD4 genome AF: 0.890 AC: 135462 AN: 152132 Hom.: 60490 Cov.: 32 AF XY: 0.887 AC XY: 66000 AN XY: 74370

African (AFR) AF: 0.931 AC: 38671 AN: 41536

American (AMR) AF: 0.900 AC: 13749 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2947 AN: 3470

East Asian (EAS) AF: 0.996 AC: 5149 AN: 5170

South Asian (SAS) AF: 0.857 AC: 4133 AN: 4824

European-Finnish (FIN) AF: 0.803 AC: 8497 AN: 10584

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.874 AC: 59392 AN: 67960

Other (OTH) AF: 0.875 AC: 1847 AN: 2112

Alfa AF: 0.894 Hom.: 41332

Bravo AF: 0.902

Asia WGS AF: 0.915 AC: 3183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	12
DANN	Benign	0.58
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs7141305; hg19: chr14-57052897;