rs6777810

Variant names:

• chr3-100528298-C-T
• rs6777810
• NM_018004.3:c.-3-26911C>T

Variant summary

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

The NM_018004.3(TMEM45A):​c.-3-26911C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,040 control chromosomes in the GnomAD database, including 26,543 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 0.57 (26543 hom., cov: 32)
• Consequence: TMEM45A NM_018004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.521
• Publications: 9 publications found

Genes affected

TMEM45A (HGNC:25480): (transmembrane protein 45A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018004.3. 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
	TMEM45A	NM_018004.3	MANE Select	c.-3-26911C>T		intron	N/A	NP_060474.1	Q9NWC5
	TMEM45A	NM_001363876.2		c.45+8690C>T		intron	N/A	NP_001350805.1	J3KQ06

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM45A	ENST00000323523.8	TSL:1 MANE Select	c.-3-26911C>T		intron	N/A	ENSP00000319009.4	Q9NWC5
	TMEM45A	ENST00000403410.5	TSL:5	c.45+8690C>T		intron	N/A	ENSP00000385089.1	J3KQ06
	TMEM45A	ENST00000860730.1		c.-4+8690C>T		intron	N/A	ENSP00000530789.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87098 AN: 151924 Hom.: 26503 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.574 AC: 87198 AN: 152040 Hom.: 26543 Cov.: 32 AF XY: 0.575 AC XY: 42690 AN XY: 74302

African (AFR) AF: 0.776 AC: 32191 AN: 41470

American (AMR) AF: 0.638 AC: 9747 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2036 AN: 3472

East Asian (EAS) AF: 0.364 AC: 1883 AN: 5168

South Asian (SAS) AF: 0.474 AC: 2286 AN: 4820

European-Finnish (FIN) AF: 0.529 AC: 5589 AN: 10568

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31711 AN: 67946

Other (OTH) AF: 0.580 AC: 1226 AN: 2114

Alfa AF: 0.504 Hom.: 81706

Bravo AF: 0.594

Asia WGS AF: 0.469 AC: 1635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.3
DANN	Benign	0.68
PhyloP100		0.52
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: rs6777810; hg19: chr3-100247142;