rs1077989

Positions:

• chr14-67509105-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182526.3(TMEM229B):​c.-192+5981T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 151,852 control chromosomes in the GnomAD database, including 13,578 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 0.40 (13578 hom., cov: 30)
• Consequence: TMEM229B NM_182526.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408

Genes affected

TMEM229B (HGNC:20130): (transmembrane protein 229B) Predicted to act upstream of or within response to bacterium. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPHN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM229B	NM_001348544.2	c.-256-5554T>G		intron_variant
TMEM229B	NM_001348546.2	c.-191-21933T>G		intron_variant
TMEM229B	NM_001348547.2	c.-191-21933T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM229B	ENST00000357461.7	c.-192+5981T>G		intron_variant		2		P1
TMEM229B	ENST00000554278.6	c.-191-21933T>G		intron_variant		4		P1
TMEM229B	ENST00000555994.6	c.-256-5554T>G		intron_variant		3		P1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60270 AN: 151732 Hom.: 13570 Cov.: 30

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.397 AC: 60283 AN: 151852 Hom.: 13578 Cov.: 30 AF XY: 0.404 AC XY: 29953 AN XY: 74204

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.409

Alfa AF: 0.477 Hom.: 38439

Bravo AF: 0.391

Asia WGS AF: 0.458 AC: 1594 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs1077989; hg19: chr14-67975822;