NM_018004.3:c.589-3659C>T

Variant names:

• chr3-100565163-C-T
• rs7429915
• NM_018004.3:c.589-3659C>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.589-3659C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,964 control chromosomes in the GnomAD database, including 22,070 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 0.51 (22070 hom., cov: 32)
• Consequence: TMEM45A NM_018004.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM45A	NM_018004.3	c.589-3659C>T		intron_variant	Intron 4 of 5	ENST00000323523.8	NP_060474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM45A	ENST00000323523.8	c.589-3659C>T		intron_variant	Intron 4 of 5	1	NM_018004.3	ENSP00000319009.4
TMEM45A	ENST00000403410.5	c.637-3659C>T		intron_variant	Intron 6 of 7	5		ENSP00000385089.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78128 AN: 151846 Hom.: 22027 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.515 AC: 78231 AN: 151964 Hom.: 22070 Cov.: 32 AF XY: 0.508 AC XY: 37721 AN XY: 74256

African (AFR) AF: 0.757 AC: 31383 AN: 41474

American (AMR) AF: 0.490 AC: 7478 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1741 AN: 3472

East Asian (EAS) AF: 0.325 AC: 1677 AN: 5160

South Asian (SAS) AF: 0.297 AC: 1431 AN: 4814

European-Finnish (FIN) AF: 0.396 AC: 4170 AN: 10526

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.424 AC: 28848 AN: 67958

Other (OTH) AF: 0.518 AC: 1088 AN: 2102

Alfa AF: 0.456 Hom.: 61548

Bravo AF: 0.538

Asia WGS AF: 0.356 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.43
PhyloP100		-0.42
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: rs7429915; hg19: chr3-100284007;